2014 terachem-nuclear medicine and biology, v. 41, is. 7, p. 547-650

Abstracts for Symposium on Technetium and Other Radiometals in Chemistry and Medicine(TERACHEM 2014) September 10‐13 2014

Nuclear Medicine and BiologyAugust 2014 Volume 41 Issue 7 Pages 545‐650

14102014 Nuclear Medicine and Biology August 2014 Volume 41 Issue 7 Pages 545-650

httpwwwnucmedbiocomissueS0969-8051(13)X0014-9 314

Abstracts for Symposium on Technetium and Other Radiometals in Chemistry and Medicine(TERACHEM 2014) September 10-13 2014

Human whole-body biodistribution and dosimetry of a new PET tracer [ C]ketoprofen methylester for imagings of neuroinflammationAkihito Ohnishi Michio Senda Tomohiko Yamane Masahiro Sasaki Tomoko Mikami TomoyukiNishio Yasuhiko Ikari Hiroyuki Nishida Miho Shukuri Tadayuki Takashima Aya Mawatari HisashiDoi Yasuyoshi Watanabe Hirotaka Onoep594ndash599Published online April 14 2014Preview Abstract Full-Text HTML PDF

11

A study on nitroimidazole- Tc(CO) complexes as hypoxia marker Some observationstowards possible improvement in in vivo efficacyMadhava B Mallia Suresh Subramanian Anupam Mathur HD Sarma Sharmila Banerjeep600ndash610Published online April 24 2014Preview Abstract Full-Text HTML PDF

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ldquoThe quantification with FDG as seen by a physicianrdquo Nucl Med Biol 201340720ndash30Luigi Mansip611ndash612Published online May 1 2014Preview Abstract Full-Text HTML PDF

Organometallic technetium chemistry past present and futureRoger Alberto Henrik Braband Michael Benz Michael Felber Sebastian Imstepfp613

Hide Preview Abstract Full-Text HTML PDF

Routinely applied metallodrugs are coordination compounds and rarely of organometallic nature Cardiolitereg beingthe most mentionable exception Over the last decade bioorganometallic chemistry grew to a prosperous field towhich Tc and Re chemistry contributed essential results [1] The ldquoaquo-ionrdquo [ Tc(OH ) (CO) ] opened a realm ofchemistry fundamental and imaging oriented and in line with the concepts of bioorganometallic chemistry of stableelements Contributions of many groups in support of this statement will be highlighted

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Synthesis of fac- TcO complexes Activation of [ TcO ] by phosphonium cationsHenrik Braband Michael Benz Roger Albertop613

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The reaction of high-valent fac- TcO complexes with alkenes via (3 + 2)-cycloaddition is an innovativeapproach for the synthesis of radioconjugates [1-3] Recent developments based on the interaction ofphosphonium salts with the robust [ TcO ] anion in neutral water led to a simple procedure for the synthesis of[ TcO (tacnR)] type complexes (tacnR = 147-triazacyclononane or derivatives) Due to this new approach fac- TcO complexes are now available in high yields and purity for stereoselective labeling of biomolecules

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Imaging carbon nanotube-mediated drug delivery with Tc and InSam Groveman Simone Alidori Lynn Francesconi David A Scheinberg Michael R McDevittp613ndash614


99m 111

Carbon nanotubes (CNT) are potentially versatile drug delivery platforms due to their large aspect ratio whichallows for amplification of drug and imaging effects Furthermore this nanomaterial exhibits distinctive fibrillarpharmacology When covalently functionalized CNT can accommodate a numerous amount of different molecularcomponents designed for theranostic purposes It was demonstrated that antibodies peptides oligonucleotidesand other drugs can be appended covalently and non-covalently to CNT

Higher carbonyl cores of Tc and Re bioconjugates Prospects and limitationsAE Miroslavov GV Sidorenko AA Lumpov MYu Tyupina DN Suglobovp614


Although [M(CO) (H O) ] cations (M = Tc or Re) are convenient precursors for tethering Tc or Re tobiomolecules introduction of M(CO) core into a biomolecule requires bulky tridentate chelators or a combination ofmono- and bidentate coordination units which can negatively affect the native properties of the biomolecule Tominimize this influence we suggested technetium and rhenium penta- and tetracarbonyl cores in combination withmono- (isocyanide) and bidentate (dithiocarbamate xanthate) ligating units respectively

3 2 3+ 99m 186188

3

Synthesis and biological evaluation of TcO-MNXT as a novel tumor hypoxia imaging agentZhenxiang Li Xuebin Wang Junbo Zhangp614


99m

In the development of hypoxia imaging agents nitroimidazole derivatives are enzymatically reduced andaccumulated in hypoxic regions therefore most labeled probes for tumor hypoxia have been based onnitroimidazole analogues In order to find a novel ideal hypoxia imaging agent MNXT (metronidazole xanthate) wassynthesized and radiolabeled with Tc-GH to form the TcOndashMNXT complex The radiochemical purity of the

TcOndashMNXT complex was over 90 as measured by TLC It was stable over 6 h at room temperature 99m 99m

99m

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[CpM(CO) ] (M = Re Tc) labeled phenylbenzothiazoles as imaging agents for Aβ plaquesJianhua Jia Mengchao Cui Boli Liup614


3 99m

The complexes of [CpM(CO) ] (M = Re Tc) conjugating the phenylbenzothiazole were synthesized andevaluated to detect amyloid-β (Aβ) deposition in the brain The rhenium complexes 1ndash4 were proved to havemedium affinity for Aβ aggregates (K = 142 76 64 and 24 nM respectively) by in vitro binding assays Tccomplexes clearly marked Aβ plaques on brain sections of Tg mice by in vitro autoradiography which confirmed thesufficient affinities for Aβ plaques (Fig 1) However they did not show admirable property in respect of initial brainuptake (lt05 IDg) which hinders the further development of these tracers as SPECT probes for diagnosis of AD

399m

1ndash42 i99m

Synthesis and evaluation of single amino acid chelate (SAAC) tetrazine derivatives forbioorthogonal conjugation with Re TcJohn F Valliant Ramesh Patel Alyssa Vitop614ndash615


99m

The inverse electron demand [4 + 2] DielsndashAlder cycloaddition reaction between radiolabeled 1245-tetrazines andbiomolecule-derived strained alkenes has recently been used to create molecular imaging probes that generateexquisite target-to-non-target ratios [1] The advantage of this pretargeting strategy is that short-lived radioisotopescan be used to image the distribution of biomolecules such as antibodies that have slow pharmacokinetics Thework to be presented involves the preparation of isostructural Tc and Re complexes of ligands derivatized withtetrazines which can be used to tag trans-cyclooctene modified biomolecules

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Enhancing chemical properties and stability of M(CO) (M = Re Tc) complexes throughligand donor modificationsPaul D Benny Thomas R Hayes Patrice A Lyonp615


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While a number of chelates and strategies have been developed for the organometallic precursor fac-[M(OH ) (CO) ] (M = Re Tc) a unique challenge remains to improve the overall function and performance ofthese complexes formed for in vitro and in vivo applications The versatile nature of the M(CO) core resides in thefacile preparation and exchange of the aquo ligands with mono- bi- or tridentate ligands However the overallstability and lipophilic nature of the CO ligands inherently impact the pharmacodynamic behavior and in vivoclearance properties of M(CO) complexes

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Synthesis of water stable M O -N-heterocyclic carbene complexes (M = Re Tc)Michael Benz Henrik Braband Roger Albertop615

(V) 2 + 99

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Recently the scope of N-heterocyclic carbenes (NHCs) has been extended from catalytic application to the field ofbioinorganic chemistry and metals in medicine In this context the NHC chemistry of technetium came into ourresearch focus However TcndashNHC complexes are scarce [1] While Re O complexes which containmonodentate NHCs are hydrolytically stable the corresponding Tc O ndashNHC complexes show rapid hydrolysisin the presence of trace amounts of H O [2] We present novel synthetic pathways for the synthesis of water stableM O ndashNHC complexes [3]

99 (V)2

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Tc-labelling of surface localised SNAP-tag sites on a Gram positive bacteriumRamla Awais Bethany Mills Jeni Luckett Paul Williams Phil Hill Alan Perkins Philip DuncansonVaughan Griffithsp615


99m

SNAP-tag is a protein based on human O -alkylguanine-DNA alkyltransferase (hAGT) that can bind specifically andcovalently to substrates bearing an O -benzylguanine unit It has proved possible to express this protein in theGram positive bacteria Staphylococcus aureus and to specifically anchor it to the bacterial cell wall via Sortase Athus providing a potential strategy for selectively labelling these modified bacteria As preliminary data showed thatthe surface-localized SNAP tags are accessible to fluorescent probes bearing an O -benzylguanine unit in vitro wehave investigated the possibility of developing analogous radioligands

66

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Tc-labeled biotin conjugate in a tumor ldquopretargetingrdquo approach with monoclonal antibodybevacizumabN Kiza G Makris D Papagiannopoulou T Tsotakos D Mastellos C Tsoukalas P Bouziotisp615ndash616


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Vascular endothelial growth factor (VEGF) released by tumor cells is an important growth factor in tumorangiogenesis Bevacizumab is designed to directly bind to VEGF extracellulary to prevent interaction with VEGFreceptors Given the drawbacks of radiolabeled monoclonal antibodies (mAbs) such as slow blood clearance andunspecific binding to normal tissues antibody pretargeting is an approach which combines the desirable propertiesof high tumor uptake of antibodies with rapid pharmacokinetics and fast whole-body clearance of radioactivity

Characterization of Tc-caspofungin as fungal infection agent and assessment of potentialinfluence of pretreatmentLaura Reyes Leticia Fernaacutendez Moacutenica Vilche Patricia Oliver Ana Rey Mariella Teraacutenp616


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Reliable clinical interpretation of scintigraphic images for the diagnosis of fungal infections is not always simplebecause of low specificity and sensitivity of the available radiopharmaceuticals [1] Our group studies potential

99m

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radiopharmaceuticals for infection diagnosis in this particular case characterization of Tcndashcaspofunginndashtricarbonyl complex and the influence of pretreatment with caspofungin is evaluated Tcndashcaspofunginndashtricarbonylcomplex was obtained by water molecules substitution of fac-[Tc(I)(H O) (CO) ] precursor with caspofungin(MERCK) [2]

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Imidazole stabilized [2 + 1] Re(I) Tc(I) complexes as isostructural nuclear and optical probesAbdolreza Yazdani Tamil Selvi Pitchunmony Laura Banevicius Shannon Czorny John F Valliantp616


99m

The synthesis stability and photophysical properties of [2 + 1] Re(I)Tc(I) complexes of bipyridine and a series oftriazole and imidazole derivatives were investigated as a means of identifying complexes suitable for use in creatingtargeted isostructural opticalnuclear molecular imaging probes To prepare the desired complexes[Re(CO) (H O) ] was combined with 22prime-bipyridine (bipy) to give [Re(CO) (bipy)Br] which in turn was converted tothe desired complexes through the treatment with functionalized triazoles and imidazoles and heating the mixture toreflux overnight

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Labelling PAMAM dendrimers with Tc-99m via HYNICL Kovacs M Tassano M Cabrera M Fernaacutendez R Anjos P Cabral W Porcalp616ndash617


Dendrimers are branched macromolecules with a well-defined structure very low polydispersity and highfunctionality Poly(amidoamine) (PAMAM) dendrimers are the most studied class of dendrimers for biomedicalpurposes In the present study PAMAM G4 dendrimer conjugated with hydrazinonicotinamide (HYNIC) an efficientbifunctional chelator was characterized and optimized The conjugated dendrimer was labeled with Tc usingtricine coligand and the stability of the labeled complex was evaluated

99m

Re radiotherapy facilitated by virus expressing the human sodium iodide symporterJustin Ady Justin Belin Sam Groveman Yuman Fong Lynn Francesonip617


188

Rhenium-188 emits a beta with a maximum energy of 212 MeV and can be easily and relatively inexpensivelyobtained from portable W Re generators as sodium perrhenate (Na ReO ) This makes rhenium anattractive option for use in radio-cancer therapies The human sodium iodide symporter (hNIS) transports NaIacross cell membranes but it has been shown that hNIS can also transport perrhenate (ReO ) hNIS which isexpressed primarily in the thyroid glands has facilitated radiotherapy for thyroid cancer for over sixty years

188 188 1884

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Determination of optimized conditions for Tc-labeled rifampicin preparation fortuberculosis imaging applications

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Ali Badbarin Amir R Jalilian Fariba Johari Daha Mitra Athari-Alafp617


Developing new infection imaging agents is a mandate in the detection of resistant species in the clinic due to themortality of various new strains of bacteria including Mycobacterium tuberculosis Various conditions wereoptimized for the rapid and efficient labeling of rifampicin antibiotic with Tc-99m for ultimate use in infection imagingRadiochemical purities were checked by ITLC using methyl ethyl ketone normal saline on Whatman No 1 paperTime temperature ligand concentration stannous ion amount pH etc

Novel Tc-labelled estrogen derivative as potential agent for estrogen receptors imagingL Bauzaacuten S Fernaacutendez S Dematteis H Cerecetto J Giglio A Reyp617


99m

With the objective to develop a potential radiopharmaceutical for estrogen receptors imaging we have prepared andevaluated an ethinylestradiol derivative labelled with Tc99m

[ Tc(N)PNP]-scaffold for SPECT of multidrug resistance Early in-vitro studyC Bolzati V Gandin N Morellato N Salvarese C Marzano D Carpanese L Meleacutendez-Alafort ARosatop618


99m

Tc(N)-DBODC(PNP5) [DBODC = bis(N-ethoxyethyl)dithiocarbamato PNP5 = bis(dimethoxypropylphosphinoethyl)ethoxyethylamine] is a cationic mixed-compound originally investigated asmyocardial imaging agent identified as suitable scaffold to devise Tc-agents for SPECT of multidrug resistance(MDR)

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Aptamer-HYNIC- Tc A molecular imaging agent of PTK7Victoria Calzada Marcelo Fernaacutendez Joel Gonzaacutelez Mariacutea Moreno Alejandro Chabalgoity HugoCerecetto Pablo Cabral Thomas Quinnp618


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Aptamers are single-stranded oligonucleotides that recognize molecular targets with high affinity and specificityThe unique molecular recognition properties of aptamers are being developed to image protein tyrosine kinase-7(PTK7) a member of the receptor tyrosine kinase family over expressed on many cancers In this work a DNAaptamer against PTK7 was coupled with HYNIC(Tricine) and radiolabeled with technetium-99m Physicochemicaland biological controls were assayed in acute lymphoblastic leukemia CCRF-CEM cells

X

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Thiocarbamoylbenzamidines for bioconjugation of Re and TcJuan Daniel Castillo Goacutemez Nguyen Hung Huy Ulrich Abram Nicola Beindorff Winfried Brennerp618


Thiocarbamoylbenzamidines are suitable ligand systems for Re and Tc [12] However no studies regarding theirsuitability for bioconjugation with Tc have been published so far We have designed different complexes of Reand Tc with thiocarbamoylbenzamidines which possess propargylic or carboxylic groups available forbioconjugation H-NMR studies of the click-coupling products with model molecules show the disappearance of thepropargylic signal and the formation of the triazole ring as confirmed by X-Ray crystal analysis

99m99

1

Biological evaluation of two glucose derivatives radiolabeled with Tc as potential cancerimaging agentsRosina Dapueto Marcelo Fernaacutendez Rodrigo Aguiar Mariacutea Moreno Camila Machado FabioMarques Juan P Gambini Roger Chammas Pablo Cabral Williams Porcalp618ndash619


99m

The aim of this work is to develop two glucose derivatives radiolabeled with Tc in order to obtain FDG analogsfor SPECT Both derivatives were designed to contain an IDA-like chelator for complexation with Tc attached toglucose anomeric carbon (C1) or C2 Radiolabeling with Tc of compounds was accomplished by direct labelingwith high radiochemical purity controlled by HPLC Complexes also probed to be highly stable in time until 5 hoursof radiolabeling and hydrophilic according to LogP values

99m 1899m

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Radiolabeling and biological evaluation of amphotericin using fac-[ Tc(I)(H O) (CO) ]Leticia Fernaacutendez Laura Reyes Mariella Teraacutenp619


99m 2 3 3 +

Mycoses are fungal infections that usually do not cause serious illness nevertheless severe immunosuppressionmay compromise the patients life Infection identification and its discrimination from inflammation are a challengingdilemma The implications of prompt diagnosis on the appropriate management of infectious focis are vital for thepatients evolution Nuclear medicine can be an alternative using a suitable radiotracer to detect infection sites [1]

Development of a Tc(I)-tricarbonyl complex as potential agent for hypoxia imagingS Fernaacutendez J Gigio H Cerecetto A Reyp619


99m

Herein we present the development of a Tc complex bearing the 5-nitroimidazol-1-yl moiety with recognizedhypoxic selectivity as a potential radiopharmaceutical for imaging tumour hypoxia

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A novel Tc-99m-labeled lactam bridge-cyclized alpha-MSH peptide with enhanced melanomauptakeHaixun Guo Yubin Miaop619


The purpose of this study was to examine the melanoma targeting and imaging properties of Tc-labeled lactambridge-cyclized HYNIC-Aoc-Nle-CycMSH hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH peptide Methods HYNIC-Aoc-Nle-CycMSH was synthesized using fluorenylmethyloxycarbonyl (Fmoc) chemistry The melanocortin-1 (MC1) receptor binding affinities of the peptide were determined inB16F1 melanoma cells The melanoma targeting and imaging properties of Tc(EDDA)-HYNIC-AocNle-CycMSH were determined in B16F1 melanoma-bearing C57 mice

99m

hex2 hex

99m

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Synthesis and preliminary evaluation of Tc-labelled monomeric dimeric and tetramericfolate derivativesZhide Guo Manli Song Pu Zhang Chang Liu Xianzhong Zhangp620


99m

The aim of this study is to develop a new strategy for developing multimeric molecule probes used for SPECTimaging Thus multimeric concept has been used to synthesise FR-targeting imaging probes (monomeric dimericand tetrameric folate derivatives) The novel folate derivatives were radiolabelled with Tc using tricine andtrisodium triphenylphosphine-33prime3Prime-trisulfonate (TPPTS) as coligands and resulted in three Tc-complexes( Tc-HYNIC-D -PEG-FA Tc-HYNIC-D -PEG-FA Tc-HYNIC-D -PEG-FA )

99m99m

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99m1 2

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Theoretical study of Re and Tc DMSA complexesDaniel Hernaacutendez-Valdeacutes Alejandro Blanco-Gonzaacutelez Zalua Rodriacuteguez-Riera Ulises Jauacuteregui-HazaLuis Ducat-Pages Luis Pizarro-Loup620


Meso-23-dimercaptosuccinic acid (DMSA) is used in nuclear medicine as ligand for the preparation ofradiopharmaceuticals for diagnostic and therapy DMSA has been the subject of numerous investigations during thepast three decades and lots of new and significant information on the chemistry and pharmacology of DMSAcomplexes have emerged In comparison to other ligands the structure of many DMSA complexes is unclear up totoday The structures and applications of DMSA complexes are strictly dependent on the chemical conditions oftheir preparation especially pH and the ratio of components

Computational study of Re and Tc tricarbonyl complexesDaniel Hernaacutendez Valdeacutes Zalua Rodriacuteguez Riera Ulises Jaacuteuregui Haza Claude Picard Eric Benoistp620

X

X

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The development of novel radiopharmaceuticals in nuclear medicine based on the M(CO) (M = Tc Re) complexeshas attracted great attention The versatility of this core and the easy production of the fac-[M(CO) (H O) ]precursor could explain this interest The main characteristics of these carbonyl complexes are a high substitutionstability of the three CO ligands and a corresponding lability of the coordinated water molecules yielding via easyexchange of a variety of mono- bi- and tridentate ligands complexes of very high kinetic stability

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Preparation and biological evaluation of a Tc labelled fibroblast activation protein inhibitorP Iveson R Ahmad M Bapat M Morrison A Olsson A Meijerp620


99m

The synthesis Tc labelling and biological evaluation of a tetraamine derivatised fibroblast activation protein(FAP) inhibitor (GEH200200) are reported In vitro studies using the analogous rhenium complex showed goodaffinity for FAP (IC 9 mM) and gt3000 selectivity for FAP over DPP-IV Tc-GEH200200 was formed rapidly inhigh yield at room temperature HPLC purified Tc-GEH200200 was used for in vivo studies in naiumlve ratsMetabolism studies showed that 80 of the parent Tc-GEH200200 was still present in plasma at 60 min pi

99m

5099m

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Tc(CO) -labeled 2-phenylbenzothiazoles as Aβ imaging agents for the detection of CAAJianhua Jia Mengchao Cui Boli Liup620ndash621


99m 3

Cerebral amyloid angiopathy (CAA) is related to the deposition of β-amyloid (Aβ) on blood vessel walls of brain Tospecifically detect Aβ in CAA TcRe complexes were prepared and evaluated 24 displayed high affinity for Aβaggregates (K = 42 nM) The high affinity of [ Tc]24 for Aβ was certified by in vitro autoradiography on brainsections of Tg and AD Interestingly [ Tc]24 could only label Aβ in blood vessels (white triangle) but not Aβ inparenchyma (gray arrow) of the AD brain (Fig

99m

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Synthesis and biodistribution of TcO-TRYDTC as a novel potential tumor imaging agentJingjing Zhu Qiran Hu Jin Du Xuebin Wang Junbo Zhangp621


99m

There has been an increasing interest on a wide range of radiolabeled amino acids because they are thesubstrates of various amino acids transport systems which can be upregulated in certain tumors L-tyrosine is anatural amino acid and its molecular structure has an active amine group thus making it possible to react withcarbon disulfide in NaOH solutions to produce the corresponding dithiocarbamate In this study tyrosinedithiocarbamate (TYRDTC) ligand was successfully synthesized and then radiolabeled with [ TcO] core toproduce TcO-TYRDTC with high radiochemical purity

99m 3+99m

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Synthesis and biodistribution of Tc(CO) -G12N3 as a potential agent for tumor imagingTeli Liu Xuebin Wang Junbo Zhangp621


99m 3

Carbohydrates especially glucose are the main energy resource of living beings It accumulates in some metabolicvigorous cells and tissues transported by glucose transporters (GLUTs) As for tumor imaging Tc labeledglucose derivatives are considered to be of great interest In order to get a good tumor imaging agent wesynthesized a new glucose analogue (G12N3) by lsquoclick chemistryrsquo with glucose-azide and alkyne-[12]aneN (amacrocyclic polyamine) The G12N3 ligand for labeling with Tc through the formation of a Tc(CO) complexwas successfully synthesized

99m

399m 99m

3

Synthesis and biodistribution of Tc(CO) -CPADG as a promising tumor imaging agentYue Wang Jingjing Zhu Xiaoqing Song Xuebin Wang Junbo Zhangp621


99m 3

[ F]fluorodeoxyglucose [ F]FDG is the most widely used positron emission tomography (PET)radiopharmaceutical all over the world However the high costs related to its production and the need for acyclotron nearby are realistic limitations Therefore using Tc to label glucose analogues is still the major focus ofradiopharmaceuticals research Up to now the [ Tc(CO) ] core has become a valuable alternative to the state ofthe art Tc labeling techniques thus encouraging us to synthesize the Tc(CO) complex for finding a goodtumor imaging agent

18 18

99m99m

3+

99m 99m3

Tc-gastrins Impact of (Glu) -chain and NEP-inhibition on pharmacokineticsA Kaloudi BA Nock E Lymperis EP Krenning M de Jong T Mainap622


99m 5

Gastrin-based Tc-radiotracers like [ Tc]SG6 = [( Tc-N )Gln ]gastrin show higher metabolic stability andCCK2R-positive tumor targeting compared to des-(Glu) -truncated analogs such as [ Tc]DG4 = [( Tc-N )DGlu ]gastrin(10ndash17) However the (Glu) -chain is implicated in high renal uptake We herein compare theeffect of neutral endopeptidase (NEP) inhibition by phosphoramidon (PA) on the bioavailability andpharmacokinetics of [ Tc]SG6 and [ Tc]DG4 in mice Blood collected 5 min post-injection (pi) of either[ Tc]SG6 or [ Tc]DG4 in mice without or with PA (300 μg) coinjection was analyzed by HPLC

99m 99m 99m4

1

599m 99m

410

5

99m 99m99m 99m

Imaging of VEGF expression with Tc(I) and Tc(V) bevacizumab conjugatesN Kiza C Tsoukalas T Tsotakos S Xanthopoulos M Paravatou-Petsotas G Kastis P Bouziotisp622


99m 99m

X

X

X



Vascular endothelial growth factor (VEGF) is considered to be a major angiogenic factor responsible for thedevelopment of tumor vasculature Tc is the most popular radionuclide for clinical imaging because it has idealnuclear properties The aim of this study was to image VEGF expression with Tc-labeled anti-VEGF antibody(bevacizumab) non-invasively

99m99m

Metastatic melanoma targeting property of a novel Tc-99m-labeled HYNIC-conjugated lactambridge-cyclized alpha-MSH peptideLiqin Liu Yubin Miaop622


The purpose of this study was to determine the metastatic melanoma targeting property of the novel Tc(EDDA)-HYNIC-AocNle-CycMSH hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH peptide that we have identified Methods HYNIC-Aoc-Nle-CycMSH was synthesized usingfluorenylmethyloxy carbonyl (Fmoc) chemistry The melanocortin-1 (MC1) receptor binding affinities of the peptidewere determined in B16F10 melanoma cells The melanoma targeting and imaging properties of Tc(EDDA)-HYNIC-AocNle-CycMSH were determined in B16F10 pulmonary metastatic melanoma-bearing and normal C57mice

99m

hex2 hex

99m

hex

Synthesis and biodistribution of Tc-HYNIC-DG as a novel potential tumor imaging agentLiqin Liu Manchen Zhao Zhuo Wang Yuanyan Qin Xuebin Wangp622ndash623


99m

In this study a conjugate of 6-hydrazinopyridine-3-carboxylic acid (HYNIC) with the D-glucosamine hydrochloride(DG) was synthesized though a multiple-step reaction The structure of ligand HYNIC-DG was confirmed by HNMRand MS HYNIC-DG could be labeled successfully and efficiently with Tc using N-[2-hydroxy-11-bis(hydroxymethyl)ethyl]glycine (tricine) and ethylenediamine-NNprime-diacetic acid (EDDA) as co-ligands to form

Tc-HYNIC-DG in high yields (gt95) The partition coefficient and electrophoresis results indicated it was veryhydrophilic and electronegative

199m

99m

Copolymer based radiotracers for liver ASGP-R targeted SPECT imagingChang Liu Zhide Guo Pu Zhang Xianzhong Zhangp623


Asialoglycoprotein receptor (ASGP-R) is a well-known cell surface receptor specific for liver present in normalmammalian hepatocyte membrane Detection of its number and activity is an excellent method for evaluating thestatus and function of liver [1] Copolymer based radiotracers with controllable ratio of targeting moiety (VLA) weredeveloped as potential ASGP-R targeted imaging agents P(VLA-co-VNI) were synthesized by free-radicalcopolymerization and lyophilized for Tc instant kit labeling with high yield and RCP (gt99) [2] 99m

X

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1 2 3 Next gt

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New GRPR-antagonists mimicking [ Tc]Demobesin 1T Maina A Nikolopoulou R Cescato D Charalambidis B Waser E Ketani JC Reubi BA Nockp623


99m

We have previously reported on the GRPR-antagonist [ Tc]Demobesin 1 [ Tc]DB1 ( Tc-[N4prime-dig-DPhe Leu-NHEt ]BBN(6ndash13)) which shows superior biological profile and in particular a higher uptake in PC-3xenografts in mice than analogous agonist-based Tc-radioligands We now present a small library of[ Tc]DB1 mimics by performing strategic structural modifications in a) the spacer ([ Tc]DB2 [ Tc]DB7 and[ Tc]DB8) b) the C-terminus ([ Tc]DB9 and [ Tc]DB10) and c) the peptide chain ([ Tc]DB11 and[ Tc]DB12)

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99m99m 99m 99m99m 99m 99m 99m99m

New [ Tc(CO) (NSN)] chelate conjugated to a somatostatin receptor-seeking peptideGeorge Makris Lauren Radford Fabio Gallazzi Silvia Jurisson Heather Hennkens DionysiaPapagiannopouloup623


99m 3 +

Chelating Tc to a somatostatin receptor (SSTR)-seeking peptide may allow targeted delivery of this attractivediagnostic radionuclide to neuroendocrine cancers that over-express SSTRs We present here the synthesis of anovel tridentate bifunctional chelator 3-(2-aminoethylthio)-3-(1H-imidazol-4-yl)propanoic acid L its pyrrolidineamide derivative Lpyr and the Lsst -ANT bioconjugate where the SSTR-seeking peptide sst -ANT (4-NO -Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH ) is linked to L via the N-terminus

99m

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httpwwwnucmedbiocomissueS0969-8051(13)X0014-9page=1 115

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Issue 7 August 2014 p545-650

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Volume 41 Issue 7 p545-650August 2014

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Synthesis and biological evaluation of novel bone-seeking [Re Tc(CO) ] complexesGeorge Makris Ioannis Pirmettis Minas S Papadopoulos Dionysia Papagiannopouloup623ndash624


99m 3

Radiolabelled bisphosphonates such us Tc-MDP and Re Re-ΗΕDP bind to bone matrix carrying γ or βradiation and are used for bone imaging or bone pain palliation respectively In our work we describe the synthesischaracterization and biological evaluation of novel complexes of the type fac-[Re Tc(CO) (κ -L)] Re TcL1Re TcL2 Re TcL3 Ligands L1ndashL3 were synthesized by incorporating a different tridentate chelator on thebone-seeking pharmacophore 1-(3-aminopropylamino)ethane-11-diyldiphosphonic acid di-(2-picolyl)amine in L1iminodiacetic acid in L2 and 2-picolylamine-N-acetic acid in L3

99m 186 188

99m3

3 99m99m 99m

99m

Articles amp Issues For Authors Journal Info SRS Subscribe More Periodicals

X



New Tc-radioimmunoconjugates for pancreatic carcinoma detectionLaura Meleacutendez-Alafort Cristina Bolzati Gaia Zuccolotto Giulio Fracasso Nicola Salvarese MarcoColombatti Antonio Rosatop624


99m

Pancreas carcinoma is responsible for more than 30 of tumor-related death because it is notoriously difficult todiagnose thus new diagnostic approaches are imperatively needed Recently prostate stem cell antigen (PSCA)and mesothelin demonstrated high expression and wide distribution in pancreatic cancer but not in normalpancreas This research aims to develop new radioimmunoconjugates (RICs) for pancreatic cancer detection basedon monoclonal antibodies (mAb) to PSCA and mesothelin which are heavily overexpressed in this tumor histotype

Development and preliminary biological study of radiopharmaceutical for radiosynovectomylabelled by ReOE Klementyeva AO Malysheva GE Kodina NA Taratonenkova MV Zhukovap624


188

Radiosynovectomy is a therapy used to relieve pain and inflammation from rheumatoid arthritis and relateddiseases Progression of the disease leads to the destruction of the joint or loss of function In this study the Re-Sn suspension was synthesized and characterized according to its physico-chemical properties and biologicalbehavior in rabbits

188

Synthesis of novel rhenium and technetium N O schiff base complexesKM Reinig DA Rotsch LL Radford EM Weis AB Taylor CL Barnes SS Jurissonp624


2 2

Technetium-99m Schiff base complexes more commonly known as the ldquoQ-seriesrdquo have been considered for useas single photon emission computed tomography (SPECT) imaging agents Rhenium is often a structural analogueto technetium and has isotopes ideal for radiotherapy and imaging therefore Re- and Tc-Schiff base chemistry hasbeen investigated

Synthesis of Tc analogue of I-mIBG for possible use in neuroendocrine tumorimagingNavin Sakhare Soumen Das Anupam Mathur VV Murhekar R Krishna Mohan G Prabhakar SSSachdevp624ndash625


99m 123131

Introduction Radio-iodine ( I I) labeled meta-iodobenzylguanidine (mIBG) is a popular radiopharmaceuticalused worldwide for diagnosis of neuroendocrine tumors particularly adrenal medullae related tumors However

123 131

123 131

X

X

X

X



limited availability of I and non-ideal diagnostic nuclear characteristics of I necessitate the need for a rationalesubstitute Tc has been the clinical choice due to its ideal nuclear characteristics and easy availability Hence anattempt has been made to synthesize a Tc analogue of mIBG using 4 + 1 labeling approach and subsequentlyevaluating its efficacy for the aforementioned application

123 13199m

99m

Tc -based mixed complexes for the design and the development of new SPECT tracersN Salvarese N Morellato A Dolmella L Meleacutendez-Alafort D Carpanese A Rosato F RefoscoC Bolzatip625


III

The trivalent state is the most stable oxidation state of technetium and rhenium however none of theradiopharmaceuticals currently in clinical use contains the metal in this oxidation state We present here a generalprocedure for the preparation of a series of six-coordinated mixed ligand [ Tc (PS) (L )] compounds (PS = phosphino-thiolate L = dithiocarbamate) to design a new class of Tc -imaging agents

9999m III2

nn III

Biodistribution of 80 nm iron oxide nanoparticles labeled with Tc in Balbc miceSaeed Shanehsazzadeh Afsaneh Lahootip625


99m

Introduction Recently ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs) have been widelyused for medical applications One of their important applications is using these particles as MRI contrast agentThe aim of this study was to evaluate the biodistribution of dextran coated iron oxide NPs labeled with Tc with80 nm hydrodynamic size via intravenous injection in Balbc mice

99m

(2-Hydroxyphenyl)diphenylphosphine as fac-[Re Tc(CO) ] -ligandA Shegani C Triantis F Tisato V Peruzzo B Nock T Maina C Raptopoulou V Psycharis IPirmettis M Papadopoulosp625ndash626


99m 3 +

Mixed ligand fac-[ML L (CO) ] (M = Tc(I) Re(I)) complexes containing a monoanionic bidentate L and amonodentate ligand L are particularly interesting for the development of new radiopharmaceuticals Coupling of avector to one ligand and tuning of pharmacokinetics with the other provide unique design versatility In this work wehave studied (2-hydroxyphenyl)diphenylphosphine (POH) as a ligand to the fac-[Re Tc(CO) ] -fragment Inequimolar amounts POH readily reacts with the [NEt ] [ReBr (CO) ] precursor to afford fac-[Re(PO)(H O)(CO) ]1

1 23

21

99m3

+

4 2 3 3 2 3

Neutral fac-[Re(I) Tc(I)(CO) ] -complexes with the new POL-donor systemA Shegani C Triantis F Tisato V Peruzzo B Nock T Maina C Raptopoulou V Psycharis I

99m 3 +

X

X

X



Pirmettis M Papadopoulosp626


We have recently investigated potential means toward neutral mixed-ligand fac-[ML L (CO) ] (M = Tc(I) Re(I))complexes containing the (2-hydroxyphenyl)-diphenylphosphine (PO ) ligand (L ) For such purposes the fac-[Re Tc(PO)(H O)(CO) ] precursor (1) has been synthesized after reaction of equimolar amounts of POH with[NEt ] [ReBr (CO) ] In this work we have further investigated the substitution of labile H O-molecule in 1 by amonodentate ligand L such as imidazole (im) isocyanide (isc) and pyridine (py)

1 23

minus 299m

2 34 2 3 3 2

1

Mixed pharmacophore fac-[M(OO)(isc)(CO) ] (M = Re Tc) complexesCharalampos Triantis Marina Sagnou Barbara Mavroidi Maria Paravatou-Petsotas IoannisPirmettis Minas Papadopoulos Maria Pelecanoup626


3 99m

Tricarbonyl fac-[M(OO)(isc)(CO) ] (M = Re Tc) complexes with the β-diketones acetylacetone or curcumin asthe OO bidentate ligands and cyclohexyl isocyanide as the monodentate ligand give stable neutral complexes [1]Herein two new fac-[Re(OO)(isc)(CO) ] complexes of acetylacetone and curcumin are presented with the N-(4-benzothiazol-2-yl-phenyl)-3-isocyano-propionamide as the isc monodentate ligand In these complexes the 2-(4prime-aminophenyl)benzothiazole pharmacophore known for its anticancer as well as β-amyloid binding properties isintroduced adequately distanced from the tricarbonyl core to allow for interaction with putative binding sites ortissues

399m

3

New cis-[Re Tc(NO)(P)(isc)(CO) ] mixed ligand complexesC Triantis A Shegani C Raptopoulou V Psycharis M Pelecanou I Pirmettis M Papadopoulosp626


99m 2

The synthesis and characterization of new dicarbonyl cis-[Re Tc(NO)(P)(isc)(CO) ] complexes where thebidentate ligand is quinaldic acid (NO) and the monodentate ligands are triphenylphosphine (P) and cyclohexylisocyanide (isc) are described Reaction of the [NEt ] [ReBr (CO) ] precursor with quinaldic acid results in theformation of the aqua complex fac-[Re(NO)(H O)(CO) ] 1 which reacts readily at room temperature with equimolarquantity of cyclohexyl isocyanide to produce the mixed ldquo2 + 1rdquo ligand complex fac-[Re(NO)(isc)(CO) ] 2

99m2

4 2 3 32 3

3

New trans-cis-[Re(NO)(isc) (CO) ] and [Re(NO)(isc) (CO)] mixed ligand complexesC Triantis A Shegani C Raptopoulou V Psycharis M Pelecanou I Pirmettis M Papadopoulosp626ndash627


2 2 3

Our interest in new mixed ligand systems for the tricarbonyl fac-[Re(CO) ] core has led us to investigate thequinaldic acidisocyanide combination We present herein the synthesis and characterization of the mixed ligand

3+

X

X

X

X



complexes fac-[Re(NO)(isc)(CO) ] trans-cis-[Re(NO)(isc) (CO) ] and [Re(NO)(isc) (CO)] where NO is thebidentate ligand quinaldic acid and isc is the monodentate ligand cyclohexyl isocyanide Reaction of the[NEt ] [ReBr (CO) ] precursor with quinaldic acid results in the formation of the aqua complex fac-[Re(NO)(H O)(CO) ] which reacts readily at room temperature with equimolar quantity of cyclohexyl isocyanide to produce the ldquo2 + 1rdquo mixed ligand complex fac-[Re(NO)(isc)(CO) ]

3 2 2 3

4 2 3 3 23

3

Phosphite phosphine and arsine as ligands for fac-[Re Tc(quin)(H O)(CO) ]C Triantis A Lazopoulos A Panagiotopoulou C Raptopoulou V Phycharis M Pelecanou IPirmettis M Papadopoulosp627


99m 2 3

In order to investigate new mixed ligand systems for the fac-[Re Tc(CO) ] core the fac-[Re Tc(quin)(H O)(CO) ] precursor ndash containing the NO bidentate quinaldic acid (quinH) ndash was synthesized and reacted withphosphites phosphines and arsines as monodentate L ligands Specifically in this work we present the synthesisand characterization of the new fac-[Re(quin)(L)(CO) ] complexes where L is trimethylphosphitetris(hydroxymethyl)phosphine or triphenylarsine Reaction of the precursor fac-[Re(quin)(H O)(CO) ] 1 with theeach of the L ligands in methanol resulted in the formation of the corresponding mixed ligand complex fac-[Re(quin)(L)(CO) ] 2ndash4 in high yield

99m3

+ 99m2

3

32 3

3

A new kind of imaging agent for myocardial fatty acids metabolismTian Xue Xiang Li Jianping Liu Huabei Zhangp627


Thiophene group was introduced at the ω-position of the long fatty acids with an expectation to increasing theretention time and uptake in the heart and reducing the blood bottom Tc-CpTODTPM Tc-CpTODTBM

Tc-CpTOHTPM Tc-CpTOHTBM and their references CpTReODTPM CpTReODTBM CpTReOHTPMCpTReOHTBM were designed and synthesized respectively through a traditional methodndashdouble ligand transferreaction The radiolabeling yields of these compounds were from 10 to 15 The stability for these compoundswas very good they existed in their original form when they are put in SD rat serum for 3 h at 37 degC and NS at roomtemperature for 3 h

99m 99m99m 99m

Introduction of a hydrocarbon beta-ala linker reduced the renal uptake of Tc-99m-labeled Arg-Ala-Asp-conjugated alpha-MSH peptideJianquan Yang Yubin Miaop627


It is highly desirable to reduce the high renal uptake of Tc-RAD-Lys-(Arg )CCMSH (9297 plusmn 2172 IDg at 2 hpost-injection) which we reported previously The purpose of this study was to examine whether the replacement ofthe Lys linker with a βAla linker could decrease the renal uptake of Tc-RAD-βAla-(Arg )CCMSH Methods The

99m 11

99m 11

3410 7 11 11

X

X

X



RAD motif cyclic(Arg-Ala-Asp-DTyr-Asp) was coupled to [Cys D-Phe Arg ]α-MSH (Arg )CCMSH viaa βAla linker to generate the novel RAD-βAla-(Arg )CCMSH peptide

3410 7 113ndash13

1111

Synthesis and preclinical evaluation of novel Pteroy-lys derivatives labeled with Tc for FR-positive tumor imagingQian Yu Yuan Chen Chun Zhang Yingfang He Jie Lup627ndash628


99m

Introduction The purpose of this study was to develop novel Tc-labeled folate receptor targeting tumor imagingagents with optimal characteristicsMethods Two novel HYNIC-conjugated Pteroyl-lys derivatives with hydrophiliclinkers HYNIC-penta-lys-Pteroyl 1 and HYNIC-GlyGly-lys-Pteroyl 2 were designed synthesized and radiolabeledwith Tc using TricineTPPTS as coligands Biological evaluations of the two Tc-labeled complexes wereperformed with FR-positive KB cell lines and athymic nude mice bearing KB tumors

99m

99m 99m

Single-domain antibodies Next-generation targeting vectors for molecular imagingKristof Zarschler Katja Zscheppang Franz Kapplusch Nils Cordes Holger Stephanp628


Single-domain antibodies (sdAbs) provide significant benefits over conventional antibodies and fragments thereof interms of size stability solubility as well as tumour uptake and blood clearance Thus sdAbs have been identifiedas valuable next-generation targeting moieties for molecular imaging and drug delivery in the past years Sincethese probes are much less complex than conventional antibody fragments bacterial expression represents a facilemethod for production of sdAbs in large amounts as soluble and functional proteins

A possible mechanism for trapping Tc-HL91 in hypoxic tumorLin Zhu Wenbo Fan Yan Zhang Jinping Qiaop628


99m

Introduction Selective trapping mechanism for Tc-HL91 a hypoxia imaging agent is still not well-definedPreviously Brauers et al [Eur J Nucl Med 24 (1997) p 943] proposed that Tc-HL91 can adopt either TcO-BnAO or TcO -BnAO form in solution We hypothesize that interconversion between these two forms may beimportant for hypoxic cell uptake of Tc-HL91 [Theor Chem Acc 2008121 271ndash278] We test this hypothesis byHPLC under different conditions in solution

99m99m

299m

The preparation and preclinical evaluation of Tc-labeled microbubbles for bimodalultrasound and SPECT imagingAimen Zlitni Afaf R Genady Nancy Janzen John F Valliantp628

99m

X

X

X




Because of its low cost and portability ultrasound (US) imaging is seeing rapid growth compared to othermodalities The ability to link targeting ligands to the surface of US contrast agents which include microbubbles(MBs) has further expanded the utility of US imaging to include molecular imaging applications Quantitativeevaluation of new targeted ultrasound agents however remains a major challenge The aim of the work to bepresented is the development of a convenient and versatile platform for the preparation and purification of targetedand technetium labeled MBs

343-(LI-12-HOPO) An alternative chelator for Zr radiopharmaceuticalsMelissa A Deri Shashikanth Ponnala Brian M Zeglis Gabor Pohl Joseph J Dannenberg Jason SLewis Lynn C Francesconip629


89

Zr is an attractive radionuclide for antibody-based PET tracers because its 7841 h half-life matches the biologicalresidence time of IgG antibodies Currently antibodies are radiolabeled with Zr using desferrioxamine B (DFO)however the observed uptake of radioactivity in the bones of mice given Zr-DFO-antibody constructs suggests invivo release of Zr [1] A better chelator for Zr could eliminate the release of the bone-seeking Zr cation invivo and produce a safer PET tracer

8989

8989 4+ 89 4+ 89 4+

A novel multivalent bifunctional siderophore chelator scaffold for radiolabeling with gallium-68based on fusarinine CChuangyan Zhai Peter Knetsch Christine Rangger Dominik Summer Michael Blatzer HubertusHaas Elisabeth von Guggenberg Roland Haubner Clemens Decristoforop629


The cyclic peptide siderophore triacetylfusarinine C (TAFC) showed excellent complexing properties for Garesulting in high specific activity and excellent metabolic stability We postulated that starting from its deacetylatedform fusarinine C (FSC) trimeric bioconjugates are directly accessible to develop novel Ga-labeled targetedradiopharmaceuticals For a proof of principle the ferric form of FSC was coupled with an α β integrin targetingRGD sequence via in situ activation using HATUHOAt and DIPEA

68

68

v 3

Synthesis of tridentate ligand Potential theranostic application of a radioarsenic trithiolcomplexAnthony J DeGraffenreid Cathy S Cutler Charles Barnes Silvia S Jurissonp629


Arsenic-72 is a 26 h half-life positron emitter (249 MeV) with nuclear properties useful for diagnostic imaging bypositron emission tomography (PET) Arsenic-77 is a 388 h half-life beta emitter (683 keV) potentially useful for

X

X

X

X



radiotherapy applications Radioisotopes of arsenic have half-lives suitable for use with antibodies as targetingvectors while traditional radionuclides C F Cu and Y do not have sufficiently long half-lives (up to 4 days)to permit chemical derivatization and in vivo localization for radioimaging or radiotherapy

11 18 64 86

Robust and efficient bifunctional chelators for Cu to target α β integrinNisarg Soni Nikunj Bhatt Gwang Il An Jeongsoo Yoop629ndash630


64 v 3

The choice of bifunctional chelator (BFC) and radioisotope is crucial for imaging of biological function Cu (t = 127 h) is a β and β emitter making it useful for both imaging and radiotherapy The accuracy of imaging with

Cu often depends on BFC and hence the importance of BFC cannot be overemphasized in terms of CundashBFCcomplex robustness in vivo

6412

+ minus64

Development of a PSMA targeting nanoparticle as PETMR multimodal imaging probeSung-Hyun Moon Bo Yeun Yang Yun-Sang Lee Dong Soo Lee June-Key Chung Jae Min Jeongp630


Development of PETMR multimodal probes for PETMR scanners is important Iron oxide nanoparticles areadequate MR imaging probes For PETMR multimodal imaging chelator introduction is necessary for radiometallabeling Additionally specific ligands and PEG chains also should be introduced for active targeting Howeverintroduction of multiple ligands on to a nanoparticle is very difficult Recently we published a straightforwardmethod for multifunctional nanoparticle preparation by encapsulation with specific amphiphiles [1]

Tumor pretargeting with DielsndashAlder A TCO derivative with improved propertiesRaffaella Rossin Sander MJ van Duijnhoven Sandra M van den Bosch Marc S Robillardp630


The reaction between mAb-trans-cyclooctene (TCO) and radiolabeled tetrazines via the DielsndashAlder reaction haspotential for pretargeted tumor imaging and radiotherapy [1] Here we present the in vivo evaluation of anoxymethylacetamide-TCO (TCOac) which is highly reactive towards tetrazines (k = 135 plusmn 01 times 10 M s ) andless hydrophobic than the TCO used previously [12] In tumor-free mice CC49-TCOac circulates longer (T = 220 h) than our previous CC49-TCO (T = 141 h) [1] most likely due to the lower hydrophobicity of TCOac

24 minus1 minus1

1212

Metal-chelating polymers developed for mass cytometry as a potential route to high activityradioimmunotherapeutic agentsDaniel Majonis Xudong Lou Olga Ornatsky Isaac Herrera Mark Nitz Mitchell A Winnik DmitryBandura Vladimir Baranov Scott D Tannerp630

X

X

X




We have developed metal-chelating polymers to enable the technology of mass cytometry Briefly mass cytometryis a bioanalytical technique for single-cell protein analysis Antibodies are tagged by the covalent attachment of ametal-chelating polymer (MCP) carrying multiple ions of one stable lanthanide isotope after which a cocktail ofdifferent antibodies is used to stain a sample of cells The cells are individually introduced into an inductivelycoupled plasma mass spectrometer (ICP-MS) and the lanthanide signal relates back to the antigen profile of eachcell

Promising prospects of Sc Sc as an in vivo generator Biological evaluation and PETimagesS Huclier-Markai C Alliot J Rousseau N Chouin M Fani P Bouziotis T Maina CS Cutler JBarbetp631


44m 44

Sc (β T = 397 h) for diagnostics Sc (β γ T = 3351 d) for therapy is a valuable alternative to Ga orCu for PET-imaging of cancer prior to Lu- or Y-based radionuclide therapy Sc has an isomeric state Sc

(T = 586 h) co-produced with Sc that can be used as an in vivo Sc Sc generator When Ga or In isused for pre-therapeutic imaging for therapeutic radionuclides such as Y or Lu different in vivo uptakeespecially in critical organs such as bone and liver is observed due to dissimilar coordination chemistry thus nottruly reflecting the pharmacokinetics of the therapeutic agent

44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177

Gallium(III) complexes with new acyclic chelators for radiopharmaceutical designFrancisco Silva M Paula C Campello Lurdes Gano Ceacutelia Fernandes Isabel C Santos IsabelSantos Jose R Ascenso M Joatildeo Ferreira Antoacutenio Paulop631


Ga-radiopharmaceuticals design is a topic of utmost importance in radiopharmaceutical chemistry due to theon growing impact of Ga in the design of PET probes as a result of the recent availability of GMP Ge Gagenerators [1] In this context we have studied cold andor radioactive Ga complexes with new N O -donor Schiffbase ligands (H L H L ) and corresponding amine derivatives (H L H L ) Ligands were obtained based on thediethylenediamine backbone and by introducing pyrazolyl and pyridyl arms at the central nitrogen atom

676868 68 68

4 22 1 2 3 2 2 2 4

Nanoparticle bioconjugates labeled with alpha emittersE Leszczuk L Janiszewska P Koźmiński A Morgenstern F Bruchertseifer A Bilewiczp631


Alpha particle emitting isotopes are in considerable interest for radionuclide therapy because of their highcytotoxicity and short path length In our studies we investigated the use of TiO nanoparticles as potential carriers2

225 213 211

X

X

X

X



for Ac Bi and gold sulphide core shell nanoparticles as vehicle for At In our experiments we tested twodifferent methods of labelling The first one was based on the possibility of forming strong bonds with radionuclideson the surface of the nanoparticles In the second one TiO nanoparticles and Au SAu core shell nanoparticleswere doped with Ac and At during the process of synthesis

225 213 211

2 2225 211

Evaluation of metallofullerens for potential use in therapyTamer Sakr Harry C Dorn Zianyuan Zhang Cathy S Cutlerp631ndash632


Therapy requires delivering toxic doses selectively to the diseased or cancer cells while sparing all normal tissuesConventional agents have resulted in low therapeutic indices due to suboptimal biodistribution where only a minuteportion of the intravenously administered drug reaches the target but large doses are delivered to normal tissuesNanoparticles are being developed as an alternative due to their size and ability to circumvent some of the hurdlesencountered with traditional agents

Acyclic chelating ligands for PET imaging of tumor hypoxia with Ga-68Caterina F Ramogida Cara L Ferreira Jacqueline F Cawthray Chris Orvig Michael J Adamp632


Recently our group has developed the linear N O chelating ligand H dedpa that binds Ga quickly and undermild conditions whilst exhibiting exceptional kinetic inertness in vitro ndash ideal properties to be incorporated into a

Ga PET imaging agent [1] Herein we report nitroimidazole (NI) derivatives of H dedpa to investigate specifictargeting of hypoxic tumor cells given that NI can be reduced and retained exclusively in hypoxic cells [2] Nine N-alkylated-NI derivatives of H dedpa and H CHXdedpa (derivative with a chiral backbone) have been synthesizedand screened for their ability to bind gallium

4 2 23+

682

2 2

Preparation of [ Ti] Ti-salan-dipicGregory W Severin Andreas I Jensen Jesper Fonslet Fedor Zhuravlevp632


45

We report the carrier-free radiochemical synthesis of a neutral bio-active titanium-45 complex [ Ti]Ti-salan-dipicIn 2012 the Huhn group at Universitaumlt Konstanz reported the non-radioactive compound Ti-salan-dipic anddemonstrated therapeutic efficacy in a xenograft cervical cancer mouse model as well as enhanced in-vitrocytotoxicity over several other titanium-based chemotherapeutics [1] The mechanism of action for this class oftherapeutics is under investigation and the determination of which will be aided by radiotracing and PET with Ti

45

45

Development of Ga-PpIX peptides as fluorescencePET imaging probesNeha Sharma Babak Behnam Azad Leonard G Luyt

X

X

X



p632


The use of gallium-68 for non-invasive PET imaging has gained much interest with the increasing availability ofGe Ga generators Protoporphyrin IX (PpIX) was utilized for gallium coordination owing to its inherent

fluorescence characteristics and suitable cavity size allowing for fluorescence microscopy and PET imaging studieswith a single structural manifold PpIX was placed at the N-terminus of integrin targeting tripeptide RGD through ashort PEG linker [1] Coordination with Ga provided a fluorescent analogue that exhibited significant uptake inthe melanoma cell line MDA-MB-435 as indicated by fluorescence microscopy

68 68

6971

Bispidines as a platform for targeted multimodal imagingPeter Comba Sebastian Hunoldt Michael Morgen Jens Pietzsch Joumlrg Steinbach Holger StephanMartin Waltherp632ndash633


Ligands based on 37-diazabicyclo[331]nonane (bispidine) form very stable coordination compounds in particularwith first row transition metal ions Considering multiple functionalization bispidines are promising candidates forpharmaceutical targeting and multimodal imaging Due to the formation of thermodynamically stable and kineticallyinert Cu complexes penta- and hexadentate bispidine ligands are well suited for Cu positron emissiontomography imaging and radiotherapy ( Cu Cu)

II 6464 67

[ Cu]Cu-CryptTM ndash A novel cryptate for copper-64Christian Foerster James C Knight Melinda Wuest Brendan Rowan Suzanne E Lapi Angelo JAmoroso Peter G Edwards Frank Wuestp633


64

Objective Radiopharmaceutical evaluation of novel cryptand CryptTM for labeling with Cu64

DOTHA and NOTHA mdashNew chelates for highly efficient Cu radiolabelingS Ait-Mohand C Denis G Tremblay M Paquette B Gueacuterinp633


2 2 64

With the goal of identifying improved bifunctional chelates (BFCs) that stably complex with fast kinetics Cu wehave synthesized DOTHA and NOTHA two BFCs derived from polyazacycles and bearing methyl-hydroxamicacid pendant arms Radiolabeling experiments were performed varying the pH and the counterion and eachchelate has been compared to currently used BFCs DOTA and NOTA with respect to radiolabeling efficiency andstability DOTHA and NOTHA were prepared with great yields and ease of synthesis in solution and on solidphase

64

2 2

2 2

X

X

X

X



Kinetic inertness evaluation of copper complexes using gel electrophoresis techniquesManja Kubeil Kristof Zarschler Joumlrg Steinbach Holger Stephanp633ndash634


The development of highly stable radiocopper complexes is one major challenge that seeks to further improveradiopharmaceuticals for medicinal applications In many cases radiocopper complexes suffer the fate ofdissociation in vivo which is contributed to loss of the radionuclide resulting amongst others in an unspecificaccumulation in non-target tissues and thus in poor target-to-background ratios The kinetic lability has beenaddressed as major issue for transchelation or dissociation in vivo

Ce-DOTMP A theranostic agent for metastatic bone tumorKV Vimalnath A Rajeswari HD Sarma Sudipta Chakrabortyp634


141

Owing to its suitable decay properties Ce [T = 325 d to Pr (stable) E = 434 keV (70) 580 keV(30) E = 145 keV (485)] could be envisaged as a promising radionuclide for developing theranostic agents formetastatic bone tumor Cerium-141 was produced via Ce(nγ) Ce route with a specific activity of 200 plusmn 18 MBqmg by irradiation of natural Ce(NO ) target (8845 Ce) at a thermal neutron flux of 1 times 10 ncm s for60 d Cerium-139 and Pr are the radionuclidic impurities co-produced which could be avoided by the use ofisotopically enriched Ce target

141frac12

141β(max)

γ140 141

3 4140 14 2

143140

DFO ndash A novel octadentate BFCA for zirconium-89Malay Patra Andreas Bauman Christiane Fischer Cristiane Mari Gilles Gasser Thomas Mindtp634


Zirconium-89 ( Zr) is an emerging new metallic radionuclide with promising characteristics for PET in particular forimmuno-PET A major limitation of the use of Zr in nuclear medicine is the lack of appropriate methods for thestable chelation of the radiometal To date Zr-based imaging probes are obtained exclusively through derivativesof desferrioxamine (DFO) a chelator which does not complete the octadentate coordination sphere of theradiometal There is compelling evidence that incomplete coordination of Zr by DFO is responsible for theobserved instability of the chelate in vivo

8989

89

89

Cu-dithiocarbamate compounds for theragnostic applications Preliminary in-vitro studiesN Morellato G Cicoria V Gandin N Salvarese C Marzano C Malizia C Bolzatip634Preview Abstract Full-Text HTML PDF

64

64

X

X

X



In vitro evaluation of Cu-labeled GE11-conjugatesF Oertel F Starke W Sihver J Steinbach HJ Pietzschp634ndash635


64

The epidermal growth factor receptor (EGFR) is frequently overexpressed in epithelial tumors and consequentlyrepresents an important target for cancer diagnosis and therapy Recently a novel peptide sequence (GE11YHWYGYTPQNVI) was identified to bind the EGFR with high affinity in vitro (K = 22 nM) as well as in vivo [1]These promising data suggest that a GE11-conjugate which is radiolabeled with a positron-emitting radionuclidemay be used for the assessment of EGFR-levels of tumors and metastases by positron emission tomography thusidentifying patients which can be medicated by anti-EGFR therapy

d

Structural investigation of Ga HBED-CC complexesKarl Ploessl Zhihao Zha Seok Rye Choi Lin Zhu Hank Kungp635


nat6768

Introduction With the availability of GeGa generators Ga is becoming an isotope of choice for developing PETagents without a cyclotron Cyclic chelators such as DOTA NOTA or acyclic chelators such as NNprime-bis[2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-NNprime-diacetic acid (HBED-CC) are often used to generate functionalchelating ligands for binding Ga to bioactive organic molecules primarily because they can complex [ Ga]Ga insolution at a much faster rate than other ligands It is expected that Ga HBED-CC may form structural isomers(enantiomers and stereo-isomers)

68

68 3+3+

H octapa vs H C3octapa The difference of a single carbon atomEric W Price Brian M Zeglis Jacqueline F Cawthray Jason S Lewis Michael J Adam Chris Orvigp635


4 4

The ligands H C3octapa and p-SCN-Bn-H C3octapa were synthesized for the first time These new ligands werecompared with the previously published ligands H octapa and p-SCN-Bn-H octapa to determine whether additionof a single carbon atom to the backbone of these ligand scaffolds would effect metalradiometal chelation andstability The In and Lu complexes of H C3octapa were synthesized studied by NMR spectroscopy DFTstructure analysis potentiometric titrations and compared to the analogous H octapa complexes

4 44 4

3+ 3+4

4

Binding properties of radiolabeled cetuximab conjugatesW Sihver M Schubert H Stephan B Graham L Spiccia M Baumann J Pietzsch J SteinbachHJ Pietzschp635


The monoclonal antibody cetuximab (C225) binds with high affinity to the epidermal growth factor receptor (EGFR)

X

X

X

X



which is a major molecular target for treatment of different types of cancer Radiolabeled C225 has been proven tobe appropriate for cancer imaging and treatment This study comprises an affinity comparison of different C225conjugates incorporating p-SCN-Bn-NOTA (1) p-SCN-Bn-dipicolyl-TACN (2) and p-SCN-Bn-CHX-APrime-DTPA (3)Evaluation of the K values using homogenates of A431 cells (EGFR Her2 expression) revealed minimal lossof affinity for these conjugates compared to unchanged C225

ihigh high

PCB-TE2A-NCS A cross bridged BFC for Cu-based radiopharmaceuticalsNisarg Soni Nikunj Bhatt Gwang Il An Jeongsoo Yoop636


64

Bifunctional chelator (BFC) is a key component in developing Cu-based imaging agents For the successfuldevelopment of Cu-based imaging agents the BFC is required to make facile and strong conjugation withbiomolecule as well as to hold radiometal ions firmly in physiological conditions

6464

Peptide conjugates for EGFR-targetingK Viehweger J Hesse H Stephan L Spiccia B Grahamp636


We have synthesized Cu-labelled peptide conjugates based on a 147-triazacyclononane (TACN) framework thatmay be applied for in vivo PET imaging A peptide sequence (LARLLT ldquoD4rdquo) was used to target the epidermalgrowth factor receptor (EGFR) Overexpression and mutations of this cell-surface receptor are involved incarcinogenesis and progression of many human cancers

64

Polyacrylamide nanogel systems with Cu chelating cross-linkers for PET imagingAlexander G White Jacques Lux Minnie Chan Carolyn J Anderson Adah Almutairip636


64

In recent years increasing attention has been given to nanotechnologies within the fields of molecular imagingcombined with drug delivery We recently reported the design and synthesis of metal-chelating crosslinkersenabling formulation of polyacrylamide hydrogels (nanogels) for magnetic resonance imaging (MRI) however amajor drawback of this imaging modality is lack of sensitivity To overcome this limitation nanogels were formulatedcontaining DTPA DOTA and NOTA metal chelators for Cu-based PET imaging 64

The site-specific radiometallation of antibodies on the heavy chain glycansBrian M Zeglis Charles B Davis Robert Aggeler Brian J Agnew Jason S Lewisp636


X

X

X

X






Immunoconjugates labeled with radiometals have emerged as critical tools in nuclear medicine However the lackof site-specificity in traditional methods for the attachment of chelators can lead to poorly-defined constructs andimpair immunoreactivity To circumvent these issues we have developed a chemoenzymatic system for the site-specific radiolabeling of antibodies on the heavy chains The methodology consists of four steps (1) the removal ofterminal galactose residues on the antibody heavy chain using β-14-galactosidase (2) the incorporation of azide-modified galactosamine residues using a substrate-promiscuous galactosyltransferase (3) the strain-promoted clickconjugation of chelator-modified dibenzocycloctynes to the azide-modified sugars and (4) the radiolabeling of theresulting antibody construct

Quality control of research and GMP grade radiometals Example Lu-177CS Cutlerp637


An important aspect of manufacturing high quality radionuclides and radiopharmaceuticals for medical applicationsis establishing appropriate quality control standards and testing USP monographs exist and are being updatedwhich include specifications for radionuclide identification and assay Additionally specifications and testing must beestablished based on the criteria of the end user Important specifications include specific activity radionuclidicpurity radiochemical purity pH chemical impurities as well as pyrogenicity and sterility to name a few

Ga-Dotatate radiochemical purity impacts patient image quality 90 is not enoughM Bauwens I Pooters H Eram FM Mottaghy M van Kroonenburghp637


68

Ga-Dotatate has been extensively used in the last decade as a tool to diagnose neuroendocrine tumors There iscurrently no European monograph available but there are multiple radiosynthesis methods described in literatureas well as multiple quality control methods In the past year it has been reported that radiolysis plays a significantrole in radiochemical purity which can be as low as 76

68

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Vol 41


List of Issues



lt Previous Next gt

Phosphoramidon enhances tumor uptake of truncated [ In-DOTA]gastrinsA Kaloudi E Lymperis EP Krenning BA Nock M de Jong T Mainap637


111

Radiolabeled gastrin analogs have become attractive candidates for diagnosis and therapy of CCK2R-positivecancer We present three new analogs of [DOTA]MG11 ([(DOTA)DGlu ]gastrin(10ndash17)) whereby the oxidation-susceptible Met is substituted by Ahp (SG3) Nle (SG4) or Leu (SG5) Most importantly we report onsignificant effects induced by in vivo inhibition of neutral endopeptidase (NEP) For this purpose the potent NEP-inhibitor phosphoramidon (PA) was coinjected with the respective In-radioligands in mice

1015 15 15 15

111


X



Pharmacological characterization of α-MSH-derivativesW Sihver F Gao C Jurischka C Haase-Kohn J Steinbach D Carta C Bolzati A Calderan JPietzsch HJ Pietzschp637ndash638


The melanocortin-1 receptor is known to be overexpressed in melanoma Thus it is a potential target for novel α-MSH peptide derivatives aiming at diagnosis and therapy of melanoma In this study NOTA-NCS was conjugatedwith two peptides NAP-NS1 a linear peptide with 9 amino acids (Ahx-βAla-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH )and NAP-NS2 a lactam bridge-cyclized peptide with 12 amino acids (ε-Ahx-β-Ala-cyclo(Lys-Glu-His-D-Phe-Arg-Trp-Glu)-Arg-Pro-Val-NH ) each with the sequence His-Phe-Arg-Trp for biological activity

2

2

Evaluation of [ Ga]-DOTA ghrelin (1ndash19) in LNCaP prostate carcinomaCarlie L Charlton Savita Dhanvantari Leonard G Luytp638


68

Ghrelin is a 28-amino acid peptide that is the endogenous ligand for the growth hormone secretagogue receptor-1a(GHSR-1a) GHSR-1a is highly expressed in prostate cancer and previous work has demonstrated that ghrelindistinguishes between healthy benign and cancerous prostate tissue ex vivo We have developed a DOTA ghrelin(1ndash19) analogue capable of targeting the GHSR-1a Using orthogonal protecting groups diaminopropanoic acid-3and lysine-19 allowed for functionalization of the peptide with octanoic acid and DOTA respectively

CuCl New theranostic agentG Valentini P Panichelli C Villano G Pigotti D Martinip638


64 2

CuCl has a high tumor uptake [1] This uptake is due to an overexpression in tumor cells of the coppertransporter CTR1 [2] and probably for the increase of DNA activity replication Our aim is to evaluate the potential of

CuCl as theranostic agent in two different lines of tumors prostate cancer and uterine cancer For this reason weexamined two different patients in metastatic phase using case report method These patients presented diagnosisof metastatic lesions studied with FDG PETCT scan and CT scan

642

642

Preclinical application of Sc-folate ndash A pilot study in tumor-bearing miceCristina Muumlller Maruta Bunka Stephanie Haller Ulli Koumlster Nicholas van der Meulen AndreasTuumlrler Roger Schiblip638


47

Purpose The aim of this study was to investigate the use of Sc (T = 335 d) for β -radionuclide therapy (Eβ = 162 keV) and for SPECT imaging (Eγ = 159 keV) using a DOTA-folate conjugate

4712

minus minusav

X

X

X

X



Zr immuno-PET of epithelial ovarian cancerSai Kiran Sharma Brian Zeglis Kuntal Sevak Jason Lewis Frank Wuestp638ndash639


89

Objective To develop an immuno-PET strategy for in vivo evaluation of CA125 expression in epithelial ovariancancer

Development of HDD kit for preparation of liver cancer therapeutic agent Re-188-HDDlipiodolVinay Kumar Banka Sung-Hyun Moon Sudhakara Reddy Seelam Yun-Sang Lee Jae Min Jeongp639


Lipiodol solution of Re-4-hexadecyl-2299-tetramethyl-47-diaza-110-decanedithioacetate ( Re-HTDD) wasdeveloped for liver cancer therapy [1ndash3] However formulation of it is difficult due to multi-step syntheses and lowlabeling yield We synthesized a new compound 4-hexadecyl-47-diaza-110-decanedithioacetate (HDD) to solvethe problems HDD was synthesized from NNprime-bis-(2-hydroxyethyl)ethylenediamine BOC protection thioacetateintroduction deprotection of BOC and conjugation with 1-iodohexadecane afforded the final product

188 188

Lu-DOTA-DIISAVVGIL Labelling quality controls and in-vitro assaysN Nevares A Loacutepez Bularte M Trotta J Perez A Zapata S Michelin J Crudop639


177

HER 2 receptors (human epidermal growth factor receptor type 2) are over expressed in various human cancersincluding breast and ovarian cancers Synthetic peptides bind to these receptors with high affinity and specificityLabelled peptides with gamma or beta negative radionuclides may be useful candidates for tumour imaging or forpotential use in radionuclide therapy of cancer The aim of this work was to label DOTA-DIISAVVGIL (HER 2peptide) with Lu-177 locally produced in the RA 3 research reactor (Argentina) and carry out quality controls and in-vitro assays

Novel multivalent tracers targeting prostate cancer biomarkersRajendra Bandari Tamila Stott Reynolds Zongrun Jiang Charles Smithp639ndash640


Gastrin-releasing peptide receptors (GRPR) prostate-specific membrane antigen (PSMA) and α β integrin areidentifying biomarkers being investigated as possible tools for molecular targeting and diagnosis of prostate cancervia PET or SPECT scintigraphy The aim of this study was to investigate and compare the usage of newmultipurpose bivalent [DUPA-6-Ahx-( Cu-NODAGA)-5-Ava-BBN(7ndash14)NH ] and [RGD-Glu-[ Cu-NO2A]-6-Ahx-

v 3

642

64

X

X

X

X



RM2] radioligands for prostate cancer imaging Methods Conjugates were prepared by solid-phase peptidesynthesis purified by reversed-phase high-performance liquid chromatography metallated with CuCl and

CuCl and characterized by electrospray ionizationndashmass spectrometry

2

642

nat2

Zr labeling and preliminary evaluation of a trimeric RGD peptide based on a novelsiderophore derived chelating scaffoldChuangyan Zhai Peter Knetsch Dominik Summer Christine Rangger Hubertus Haas RolandHaubner Clemens Decristoforop640


89

Within the last years Zr has attracted increasing attention as long lived PET radionuclide So far the bifunctionalchelating system employed for Zr-applications is desferrioxamine B (DFO) Fusarinine C (FSC) a cyclic peptidesiderophore could be an alternative with potentially higher stability due to its cyclic structure having complexingproperties comparable to DFO As proof of principle in this study Zr-labelling of RGD-derivatised FSC theoptimization of analytical procedures and preliminary evaluation of this compound are reported

8989

89

Enabling simultaneous imaging and treatment with the theragnostic radionuclide Tin-117 mSuresh C Srivastavap640


The high-LET conversion electron (CE) emitter Sn-117 m (t 14 d γ 159 keV 86) shows considerable promisefor the non-invasive molecular imaging and treatment of inflammatory diseases including cancer and ofatherosclerosis caused by vulnerable plaques (VP) in the coronary and carotid arteries that when ruptured causesignificant cardiac events (~70) leading to MI and sudden death The CE from Sn-117 m is ideal for treatingVPs as their discrete range in tissue (~300 μm) is approximately the same as the VP thickness in human carotidand coronary arteries

frac12

Targeting Gastrin-Releasing Peptide Receptor-Positive Tumors using Yttrium-86 labeledDOTA-Bombesin(7-14) AnalogsN Bandara K Cherukuri S Krieger J Parry SE Lapi BE Rogersp640


The gastrin-releasing peptide receptor (GRPR) is overexpressed on a variety of human cancers including breastand prostate Bombesin (BN) is a fourteen amino acid neuropeptide that binds with high affinity to GRPR Ourlaboratory was amongst the first to evaluate BN analogues radiolabelled with positron-emitting radionuclides forimaging by positron-emission tomography (PET) The goal of this study was to evaluate DOTA-linker-BN(7ndash14)analogues radiolabelled with Y (t = 147 h β = 33 E = 664 keV) to determine the effect of using Y inplace of Cu on tumor and normal tissue uptake

8612

+avg

8664

X

X

X



Synthesis and evaluation of [ Ga]-AMD3100 A novel imaging agent for targeting chemokinereceptor CXCR4Ayoub Aghanejad Amir R Jalilian Yousef Fazaeli Behrouz Alirezapoor Mehraban Pouladi DavoudBeiki Stephan Maus Ali Khalajp640ndash641


67

In order to develop a possible CXCR4 imaging agent for oncological scintigraphy [ Ga]labeled 11prime-[14-phenylenebis(methylene)] bis-14811-tetraazacyclo-tetradecane ([ Ga]-AMD3100) was prepared using[ Ga]GaCl and AMD-3100 for 2 h at 50 degC (radiochemical purity gt95 ITLC gt99 HPLC specific activity1800ndash2000 TBqmmol) in acetate buffer Stability of the complex was checked in presence of human serum (37 degC)and in final formulation for 4 days The biodistribution of the labeled compound in vital organs of wild-type SpraguendashDawley rats were determined and compared with that of free Ga cation up to 48 h

6767

673

3+

Ga-labelled curcuminoids complexes Characterization of potential radiotracers for imagingof Alzheimers diseaseMattia Asti Erika Ferrari Stefania Croci Giulia Atti Sara Rubagotti Michele Iori Pier C CapponiAlessandro Zerbini Monica Saladini Annibale Versarip641


68

Introduction Curcumin and curcuminoids complexes labelled with F or Tc have recently shown their potentialas diagnostic tools for Alzheimers disease Herein Ga-labelled complexes with curcumin (CUR) and twocurcuminoids namely diacetyl-curcumin (DAC) and bis-dehydroxy-curcumin (bDHC) were synthesized andcharacterized Materials and methods The radiotracers were prepared by reacting Ga obtained from a

Ge Ga generator with 1 mgml curcuminoids solutions Reaction parameters (precursor amount reactiontemperature and pH) were optimized in order to obtain high and reproducible radiochemical yield and purity

18 99m68

68 3+68 68

Influence of different chelators on the radiochemical properties and imaging capabilities of a68-gallium labelled bombesin analogueMattia Asti Reneacute Martin Ralf Bergmann Michele Iori Pier C Capponi Giulia Atti Sara RubagottiAlbert Brennauer Marco Muumlller Paola A Erba Annibale Versarip641


The radiolabelled bombesin analogue AMBA shows high potential for diagnosis and treatment of prostate andbreast cancer but the influence of different chelators has not been explored so far In this study we synthesizedAMBA analogues linked to the most common used chelators DOTA NOTA and NODAGA and compared theirreactivity and in vivo biodistribution after labelling with 68-gallium

Albumin-based nanoformulation for prostate-specific membrane antigen (PSMA)

X

X

X



Sangeeta R Banerjee Baiqi Wang Mrudula Pullambhatla Catherine A Foss Martin G PomperRussell H Morganp641ndash642


Targeted delivery of nanocarriers demonstrated improved efficacy of chemotherapy while reducing its systemictoxicity Here we report a targeted albumin-based multimodality nanoformulation for potential imaging andtherapeutic delivery to prostate cancer For targeting we have selected PSMA a well-established biomarker whichexhibits high expression in primary and metastatic prostate cancer and in most solid tumor and tumorneovasculature The albumin nanoformulation was prepared by covalent conjugation of fluorescein for cell imagingDTPA for In-labeling for SPECT Glu-Lys urea for PSMA targeting and NIR dye 800 CW for in vivo opticalimaging respectively via amide bond formation and ultrafiltration after each conjugation step and characterized bymass spectroscopy and gel electrophoresis

111

Single vial kit for preparation of Ga-NODAGA-E[c(RGDfK)] as a PET radiotracerSudipta Chakraborty Rubel Chakravarty HD Sarma Ashutosh Dashp642


68 2

Cyclic RGD (Arg-Gly-Asp) peptides radiolabeled with Ga have great potential for the noninvasive monitoring oftumor growth metastasis and therapeutic response Single vial kits of NODAGA-E[c(RGDfK)] (NODAGA = 147-triazacyclononane1-glutaric acid-47-acetic acid E = Glutamic acid R = Arginine G = Glycine D = Aspartic acid f = phenyl alanine K = lysine) were formulated for radiolabeling with Ga using 10 μg of peptide conjugateRadiolabeling was performed within 5 min at room temperature by simply mixing the content of the kit vial with

GaCl (05 mL ~185 MBq)

68

2

68

683

Tumor pretargeting with antibody fragments and the DielsndashAlder reactionSander MJ van Duijnhoven Raffaella Rossin Sandra M van den Bosch Michael Wheatcroft PeterHudson Marc S Robillardp642


Cancer RIT with radiometal-labeled mAb fragments and peptides is hampered by low TK ratios due to radiometalsequestration in the kidney To overcome this drawback we evaluated whether pretargeting based on the DielsndashAlder reaction can reduce the kidney dose compared to directly labeled mAb fragments An anti-TAG72 diabody(AVP04-07) was functionalized with trans-cyclooctene (TCO) via Lys conjugation The biodistribution of I-AVP04-07 carrying respectively 0 18 and 35 TCOsdiabody (35 μgmouse) was evaluated in LS174T xenografted mice47 h post- I-diabody administration Lu-tetrazine was injected (01ndash10 eq

125

125 177

A novel radiometric phosphatidylserine (PS) binding assay based on [ Cu]Cu-NOTA-annexin-VChristian Foerster Amanda Perreault Melinda Wuest Cody Bergman Frank Wuest

64

X

X

X



p642ndash643


Objective [ Tc]Tc-HYNIC-annexin-V is currently the state-of-the-art radiotracer for in vitro and in vivo imaging ofearly stage apoptosis Here we report the application of Cu-labeled annexin-V as radiotracer in a novelradiometric binding assay to assess various phosphatidylserine (PS)-binding peptides

99m64

How technetium could help some PET nuclear chemistry technology application of Tc-99 NMRfor analysis of O-18 content in waterValery Tarasov Gayane Kirakosyan Konstantin Germanp643


The method for O and O analysis is proposed being based on addition of isotopically saturated water samplesto solid M TcO (M = NH or Na) followed by quantification of Tc-NMR spectrum fine structure in the coordinationsphere of pertechnetate The isotopic shifts ∆ ∆ NMR Tc and the constants of spin-spin interaction ofisotopomers Tc O O Tc O O Tc O O Tc O O O Tc O O are determined In the solutionof ammonium pertechnetate for the anions Tc O O and Tc O O at the temperature interval 278ndash333 К theisotopic shift is given by liner dependencies ∆ = minus0616 + 645 times 10 Т (ppm) and ∆ = minus0302 + 267 times 10Т (ppm) correspondingly

17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163

17 minus1618 minus4 1617 minus4

Receptor-mediated binding of [ Ga]tilmanocept by mesangial cellsCarl K Hoh Zhengtao Qin David J Hall David R Verap643


68

Introduction Glomerular mesangial cells regulate glomerular blood flow and provide structural support and immunesurveillance of invading pathogens This latter function is consistent with the role of CD206 the receptor for[ Tc]tilmanocept99m

Development of analytical methods for investigation of new Cu(II) complex with HL-1 ndashPotential anticancer agentD Kludkiewicz M Maurin P Garnuszek Anne-Katrin Bachon Patrick Gamez R Mikolajczakp643


64

Complex of 2-tert-butyl-6-(pyridine-2-ylhydrazonomethyl)phenol (HL-1) with copper(II) is highly cytotoxic and maybe potentially used for cancer treatment The complex was characterized with instrumental techniques and in vitroassays Replacing copper(II) with radioisotope Cu(II) may give better insight into pharmacokinetics andbiodistribution of this complex However different approach towards analysis of radioactive complex is required

64

177

X

X

X

X



Comparison of the internalization results of two minigastrin analogs labelled with LuA Loacutepez Bularte N Nevares M Trotta J Perez A Zapata S Michelin J Crudop643ndash644


177

Radiolabelled peptides with beta negative emitters are used in peptide receptor radionuclide therapy (PRRT) for thetreatment of various tumours Radiolabelled analogues of cholecystokiningastrin family showed promising resultsfor PRRT in tumour expressing CCK2 receptors

Effects of Gly DAla -replacement in GRPR-antagonist based radioligandsE Lymperis T Maina A Kaloudi EP Krenning M de Jong BA Nockp644


11 11

Radiometallated bombesin (BBN) analogs deliver diagnostic or therapeutic radiation specifically to GRPR-positivetumors such as prostate and breast cancer Based on the reported higher bioavailability of DAla -substituted BBNanalogs we developed two new GRPR-antagonists SB3 = DOTA-PABZA-DIG-[DPhe Leu-NHEt ]BBN(6ndash13) andSB4 = [DAla ]SB3 We were interested to reveal potential advantages of this single Gly DAla -replacement bycomparing the biological profiles of the two analogs and their In-radioligands

116 13

11 11 11111

Radiolabelling and preliminary biological evaluation of NOTA-cRGD dimer labelled with Ga-68Dana Niculae Ioana Esanu Filip Puicea Cosmin Mustaciosup644


The α β integrin receptor expressed on tumor cell membranes can be preferentially targeted by peptidescontaining the RGD sequence resulting in a versatile cell recognition system NOTA-SCN-Bn-E-[c(RGDyK) ] waslabelled with Ga-68 and tested for radiolabelling yield purity stability in vitro binding and ex vivo biodistributionThe radiolabelling was performed using an automated system with inline quality control and Ga-68 eluate from a tinoxide based Ge-68Ga-68 generator purified and concentrated to 400 MBq in 01 mL water on an anionicexchanger resin

v 32

A tri-modal tilmanocept for sentinel lymph node mappingZhengtao Qin Carl K Hoh David R Verap644ndash645


Introduction We report a novel method to prepare Ga and Tc dual-labeled IRDye800CW-tilmanocept asentinel lymph node (SLN) targeting agent for tri-modal molecular imaging

68 99m

89

X

X

X

X



In vivo imaging of Zr-labeled poly(2-ethyl-2-oxazoline)s and poly(ethylene glycol)sT Verbrugghen L Wyffels B Monnery R Hoogenboom S Staelensp645


89

Poly(2-alkyl-2-oxazoline)s (PAOx) are a class of versatile biocompatible polymers with promising applications indrug development

In-111 labeled peptides targeting the estrogen receptor for theranostic of cancerFilipe Vultos Ceacutelia Fernandes Joatildeo DG Correia Isabel Santos Lurdes Ganop645


Estrogen receptor (ER) expression is considered one of the most important biomarkers in breast cancer (BC)management Therefore the search for novel ER targeting ligands has been a challenging task [1]

Active targeting with Y-90 radiolabelled octreotate functionalized AGuIX ultra-small nanoparticlesM Maurin U Karczmarczyk P Garnuszek R Mikołajczak A Sawicka C Truillet F Lux AClabaut O Tillementp645


AGuIX nano particles consist of polysiloxane backbone with attached DOTA chelators These particles have beencharacterized for imaging properties after radiolabelling with In or Ga within COST TD1004 collaborationsParent AGuIX particles were functionalized with octreotate (TATE) after conjugation of peptide to terminal ammineof particle The aim of our work was to label them with Y and to evaluate their therapeutic potential

111 68

90

Radiometals development in the US Department of Energy Isotope ProgramDennis R Phillipsp645ndash646


Metallic radioisotopes are used in medicine biology environmental research nuclear forensics basic research andother important fields of scientific endeavor The practice of nuclear medicine depends upon the reliable availabilityof radioactive isotopes with the proper characteristics and sufficient quantities to support diagnostic and therapeuticresearch and clinical applications This presentation will provide a description of the congressionally mandated roleof the Isotope Program in the Office of Nuclear Physics in the U

Cyclotron based production of high specific activity [ Hg]HgCl197(m) 2

X

X

X

X



Martin Walther Stephan Preusche Hans-Juumlrgen Pietzsch Ralf Bergmann Joumlrg Steinbachp646


Hg (T = 238 h E 13398 keV 335) and Hg (T = 6414 h E 774 keV 187) are gamma-emittingradionuclides suitable for SPECT imaging and of additional interest because of the potential therapeutic us of theirAuger- and conversion electron emission The unique chemical and physical properties as metal which forms water-stable carbon-metal bonds and the easy volatility awakened interest on mercury decades ago The medical use ofmercury was virtually complete after the scientific determination of the high toxicity and long biological half life ofmercury compounds in vivo

197m12 γ

19712 γ

Production of Mn and Gd for the development of multi-modal imaging probesHeinz H Coenen Martin Buchholz Ingo Spahnp646


52g 147

The prerequisite to deploy the full potential of bi-modal PETSPECT-MR imaging is the availability of suitableradionuclides Recent research is focused on compounds of manganese and gadolinium the latter to date beinggenerally the basis of MRI contrast agents

Sc production development from Ca for radiopharmaceutical applicationM Bunka C Muumlller KA Domnanich R Schibli A Tuumlrler NP van der Meulenp646


44 44

Sc a positron emitter with a half-life of 397 h and a high positron intensity of 94 has attractive properties forpositron emission tomography (PET) and could be used as an alternative to the currently-used Ga (t = 683 min) With chemistry similar to therapeutic Y and Lu Sc can be used for diagnosis as well as for planningand monitoring of therapy before treatment with these radionuclides It is proposed that the Ca(pn) Sc nuclearreaction be used for the production of Sc [12] instead of obtaining it from a Ti Sc generator [3]

4468

1290 177 44

44 4444 44 44

Evaluation of new target materials for cyclotron production of Re and TcVernal Richards Suzanne Lapip647


186 99m

Cyclotron production of Tc and Re stands as an invaluable method to produce both radiometals This methodof preparation has become attractive to (1) combat the impending shortage of Tc due to aging reactors and (2)produce Re with higher specific activities Our proof of concept studies indicate that the use of the refractorycarbides of enriched Mo and W along with powdered Mo metal is good candidates for the cyclotronproduction of the aforementioned radiometals Unlike MoO and WO sintered targets of the refractorycarbides and metallic powder have been able to withstand the high temperatures that come with bombardment at

99m 18699m

186100 186 100

1003

1863

X

X

X

X



high beam currents for extended time periods

Large-scale cyclotron production of TcK Buckley F Benard MS Kovacs V Hanemaayer B Hook S McDiarmid SK Zeisler M DoddJ Corsaut M Vuckovic N Cockburn C Economou R Harper J Valliant TJ Ruth P Schafferp647


99m

Tc is currently supplied as the decay product of Mo produced by an aging fleet of research reactors aroundthe world Challenges to the existing supply chain are two-fold research reactors rely on enriched uranium andgenerate nuclear waste Secondly several reactors will cease operation in the next 2ndash5 years Here we report thedevelopment of a viable comprehensive solution to produce Tc in sufficient quantities to supply a large urbanarea using a conventional medical cyclotron

99m 99

99m

High purity Cu using 40ndash50 MeV protons at the Brookhaven Linac Isotope ProducerKylen Solvik Ramesh Sharma Suzanne V Smithp647


67

Copper-67 (t = 258 days) is a medically important radioisotope with potential for use in imaging and targetradiotherapy of disease It is currently produced at Brookhaven Linac Isotope Producer (BLIP) using high energyprotons (128ndash140 MeV protons) Co-production of large quantities of Cu (10 fold higher) at these high energiesrequires its decay (gt3 days) before Cu is radionuclidic pure (gt95) Co-production of a range of long-livedradionuclidic contaminates requires a three column separation method

12

6467

Development of the non-standard PET radionuclides Sc and TiHeinz H Coenen Sebastian Kuhn Ingo Spahnp647ndash648


4344g 45

For progress in medical research and practice the importance of non-standard PET radionuclides is increasing Ofthose the radionuclides Sc and Ti represent interesting examples with potential to enlarge the scope of PETtracersstudies

4344g 45

Production of Lu-177 in the BR2 high-flux reactorB Ponsardp648


The BR2 reactor is a 100 MWth High-Flux Materials Testing Reactor operated by the Belgian Nuclear Research

15 minus2 minus1

X

X

X

X



Centre SCKbullCEN The availability of high neutron fluxes up to 10 n cm s allows the routine production ofvarious radioisotopes for nuclear medicine (Mo-99Tc-99m Ir-192 Sr-89 Sm-153 Re-186 Lu-177 W-188Re-188Y-90 Sn-117m etc) In particular lutetium-177 is a very attractive therapeutic radionuclide (β E = 497 keVT = 67 d) which as well emits low energetic gamma rays (208 keV and 113 keV) for imaging

15 minus2 minus1

minusmax

12

Tc production by proton beams irradiation new excitation functions measurementSimone Manenti Luigi Gini Flavia Groppip648


99m

Tc is the most used radiotracer in nuclear medicine This is due to multiple advantages not only from a physicaland chemical point of view but also because it is conveniently available through a Mo Tc generator system99m

99 99m

PET imaging using titanium-45 Could it be usefulP Costa LF Metello F Alves M Duarte Naiap648


In the last decade a wider application of positron emission tomography (PET) as one of the most powerful medicalimaging technologies was observed This was largely due to the increased availability of equipment dedicated toproduction of radioisotopes mainly due to the installation of low energy cyclotrons in hospitals research institutesand pharmaceutical industries specialized in radiopharmaceutical production

Accelerator based Mo Tc production activity in ArmeniaR Avagyan A Avetisyan I Kerobyan R Dallakyanp648ndash649


99 99m

Experimental investigations were done for obtaining Tc by irradiation of MoO using high-intensitybremsstrahlung photons from the electron beam of the LUE50 linear electron accelerator located at YerevanPhysics Institute (YerPhI) The high value of the specific activity of Tc A asymp 3000 BqmgμAh was reached andobtained promising results The trial production (including irradiation extraction of the final product Tc fromirradiated material chemistry quality control) for Tc was established

99m nat3

99m99m

99m

Production of high purity Co at the Brookhaven Linac Isotope ProducerZachary P Gotlib Suzanne V Smithp649


57

Cobalt-57 ( Co) is an important radioisotope that has ideal characteristics for use in the calibration of a range of57

57

X

X

X

X



instruments such as point sources dose calibrators and imaging cameras We are interested to produce Co bydegrading high-energy proton beam of the Brookhaven Linac Isotope Producer (BLIP) The challenge to thisapproach is that degrading the proton energy beam results in straggle of proton energy which can result in variedproduction yields and introduce undesirable radionuclide contaminates

57

A new simple way separation of Tc from Mo targetM Gumiela E Gniazdowska P Koźmiński A Bilewiczp649


99m 100

There is growing interest in the large scale cyclotron production of Tc via the Mo(p2n) Tc reactionAdsorption chromatography enables selective elution of sodium pertechnetate from technetium generators thismethod of purification is not sufficient for many alternative production methods Extraction of technetium fromirradiated molybdenum may be carried out using either ldquowetrdquo or ldquodryrdquo chemical processes such asthermochromatography ion-exchange chromatography The aim of our studies was to elaborate a simple and fastmethod for the separation of Tc from macroscopic levels of molybdenum targets

99m 100 99m

99m

Radiation dose from cyclotron-produced Tc-radiopharmaceuticals based on theirexperimentally determined isotopic compositionSvetlana V Selivanova Johan E van Lier Eacuteric Turcotte Roger Lecomte Brigitte Gueacuterin OndrejLebeda Erik J van Lier Alexander Zyuzinp649


99m

One of the practical concerns for cyclotron production of Tc remains its radioisotopic purity and ensuing impacton radiation dose to patients

99m

Microspectrophotometry for detection of metal ion concentration of radioisotopic solutionsHayley Reed Suzanne V Smithp649ndash650


The ability to determine specific activity of the radioisotope and any contaminating metal ions of radioisotopesolution prior to release is challenging Atomic absorption spectroscopy (AAS) and inductively coupled plasmaatomic and optical emission spectroscopy (ICP-AES and ICP-OES) are very sensitive and can analyze for multiplemetal ions simultaneously Unfortunately they require relatively large quantities (up to 5 mL) of radioactivesolutions analysis takes hours and sample areas are not easily shielded

Producing high specific activity Sn-117m with acceleratorsNigel Stevenson Suresh C Srivastavap650

X

X

X




lt Prev 1 2 3



Sn-117m is a unique theragnostic isotope with excellent imaging capabilities (I = 86 159 keV SPECT photons)and therapeutic conversion electrons (I gt100 E ~140 keV) The 14 day half-life is well suited to providing a lowerdose rate over an extended period of time

X

Terachem2014-titlepdf

Slide Number 1




Human whole-body biodistribution and dosimetry of a new PET tracer [ C]ketoprofen methylester for imagings of neuroinflammationAkihito Ohnishi Michio Senda Tomohiko Yamane Masahiro Sasaki Tomoko Mikami TomoyukiNishio Yasuhiko Ikari Hiroyuki Nishida Miho Shukuri Tadayuki Takashima Aya Mawatari HisashiDoi Yasuyoshi Watanabe Hirotaka Onoep594ndash599Published online April 14 2014Preview Abstract Full-Text HTML PDF

11

A study on nitroimidazole- Tc(CO) complexes as hypoxia marker Some observationstowards possible improvement in in vivo efficacyMadhava B Mallia Suresh Subramanian Anupam Mathur HD Sarma Sharmila Banerjeep600ndash610Published online April 24 2014Preview Abstract Full-Text HTML PDF

99m 3

ldquoThe quantification with FDG as seen by a physicianrdquo Nucl Med Biol 201340720ndash30Luigi Mansip611ndash612Published online May 1 2014Preview Abstract Full-Text HTML PDF

Organometallic technetium chemistry past present and futureRoger Alberto Henrik Braband Michael Benz Michael Felber Sebastian Imstepfp613


Routinely applied metallodrugs are coordination compounds and rarely of organometallic nature Cardiolitereg beingthe most mentionable exception Over the last decade bioorganometallic chemistry grew to a prosperous field towhich Tc and Re chemistry contributed essential results [1] The ldquoaquo-ionrdquo [ Tc(OH ) (CO) ] opened a realm ofchemistry fundamental and imaging oriented and in line with the concepts of bioorganometallic chemistry of stableelements Contributions of many groups in support of this statement will be highlighted

99m2 3 3

+

Synthesis of fac- TcO complexes Activation of [ TcO ] by phosphonium cationsHenrik Braband Michael Benz Roger Albertop613

99(m) 3 + 99(m) 4 minus

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3+

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1 2 3 Next gt




99m


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99m99m 99m 99m99m 99m 99m 99m99m



99m 3 +


99m

2 2 22

X

X



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99m 3


99m 186 188

99m3

3 99m99m 99m

99m


X





99m




188


188



2 2




99m 123131


123 131

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9999m III2

nn III



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99m



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21

99m3

+

4 2 3 3 2 3


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minus 299m

2 34 2 3 3 2

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v 3




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X

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68


68

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MobileRSS Feeds


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111


1015 15 15 15

111


X






2

2



68




64 2



642

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47


4712

minus minusav

X

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4 499

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218

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11 11


116 13

11 11 11111




v 32




68 99m

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89








111 68

90





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197m12 γ

19712 γ



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4468

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44 4444 44 44



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1003

1863

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4344g 45




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57

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99m 100


99m 100 99m

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99m


99m





X

X

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lt Prev 1 2 3




X


Slide Number 1





99m3

+

99(m)4

minus99m

3+

99m3

+



99m 111





3 2 3+ 99m 186188

3



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99m

99m

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399m

1ndash42 i99m



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99m



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3+

3


(V) 2 + 99

X

X

X





99 (V)2

+(V)

2+

2(V)

2+



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66

6



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99m


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99m


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3




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188


188 188 1884

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99m


99m 99m 99m6 13

99m99m 99m 99m99m 99m 99m 99m99m



99m 3 +


99m

2 2 22

X

X



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99m 3


99m 186 188

99m3

3 99m99m 99m

99m


X





99m




188


188



2 2




99m 123131


123 131

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nn III



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+

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2 34 2 3 3 2

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68

68

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225 213 211

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45


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45


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p632




68 68

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64


d



nat6768


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68 3+3+



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X

X

X

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ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



MobileRSS Feeds


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111


1015 15 15 15

111


X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

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18 99m68

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68

2

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125 177


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99m64




17 1899

4 499

1617 1618 9916

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218

2minus

163

18 163




68




64


64

177

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11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

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X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


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1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

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15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


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57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1





3 99m


399m

1ndash42 i99m



99m


99m



3 99m


2 3 3+ 99m

3+

3


(V) 2 + 99

X

X

X





99 (V)2

+(V)

2+

2(V)

2+



99m


66

6



99m




99m


99m

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99m99m

2 3 3+



99m


3 2 3+

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99m



188


188 188 1884

4minus


99m

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99m


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1



99m


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99m

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99m


99m 99m 99m6 13

99m99m 99m 99m99m 99m 99m 99m99m



99m 3 +


99m

2 2 22

X

X



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99m 3


99m 186 188

99m3

3 99m99m 99m

99m


X





99m




188


188



2 2




99m 123131


123 131

123 131

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99m



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9999m III2

nn III



99m


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99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

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1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



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2 2 3


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3410 7 113ndash13

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99m


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99m

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89


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68

68

v 3




X

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11 18 64 86



64 v 3



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24 minus1 minus1

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44 +12

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6864 177 90 44 44m

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90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

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225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


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X

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p632




68 68

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II 6464 67



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2 2 64


64

2 2

2 2

X

X

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141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

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X

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64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



MobileRSS Feeds


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Enlarge Cover


Vol 41


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lt Previous Next gt



111


1015 15 15 15

111


X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

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2

642

nat2



89


8989

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frac12




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8664

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18 99m68

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11 11


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v 32




68 99m

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197m12 γ

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52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


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1003

1863

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X

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12

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15 minus2 minus1

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57

X

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99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1





99 (V)2

+(V)

2+

2(V)

2+



99m


66

6



99m




99m


99m

X

X

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99m99m

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188 188 1884

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1 2 3 Next gt




99m


99m 99m 99m6 13

99m99m 99m 99m99m 99m 99m 99m99m



99m 3 +


99m

2 2 22

X

X



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99m 3


99m 186 188

99m3

3 99m99m 99m

99m


X





99m




188


188



2 2




99m 123131


123 131

123 131

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123 13199m

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9999m III2

nn III



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1 23

21

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minus 299m

2 34 2 3 3 2

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3 99m


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68

68

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6412

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225 213 211

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X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

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64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1




99m99m

2 3 3+



99m


3 2 3+

3




99m



188


188 188 1884

4minus


99m

X

X

X








99m




99m


99m

99m



99m


X

X

X

X






99m99

1



99m


99m 1899m

99m



99m 2 3 3 +




99m


99m

X

X

X

X






99m

hex2 hex

99m

hex



99m


99m99m

99m0 1

99m1 2

99m2 4





X

X

X





33 2 3

+



99m


99m

5099m

99m99m



99m 3


99m

i99m

99m



99m


99m 3+99m

X

X

X

X





99m 3


99m

399m 99m

3



99m 3


18 18

99m99m

3+

99m 99m3



99m 5


99m 99m 99m4

1

599m 99m

410

5

99m 99m99m 99m



99m 99m

X

X

X




99m99m




99m

hex2 hex

99m

hex



99m



199m

99m




X

X

X

X




1 2 3 Next gt




99m


99m 99m 99m6 13

99m99m 99m 99m99m 99m 99m 99m99m



99m 3 +


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99m3

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99m


X





99m




188


188



2 2




99m 123131


123 131

123 131

X

X

X

X




123 13199m

99m



III


9999m III2

nn III



99m


99m



99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

X






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

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642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1








99m




99m


99m

99m



99m


X

X

X

X






99m99

1



99m


99m 1899m

99m



99m 2 3 3 +




99m


99m

X

X

X

X






99m

hex2 hex

99m

hex



99m


99m99m

99m0 1

99m1 2

99m2 4





X

X

X





33 2 3

+



99m


99m

5099m

99m99m



99m 3


99m

i99m

99m



99m


99m 3+99m

X

X

X

X





99m 3


99m

399m 99m

3



99m 3


18 18

99m99m

3+

99m 99m3



99m 5


99m 99m 99m4

1

599m 99m

410

5

99m 99m99m 99m



99m 99m

X

X

X




99m99m




99m

hex2 hex

99m

hex



99m



199m

99m




X

X

X

X




1 2 3 Next gt




99m


99m 99m 99m6 13

99m99m 99m 99m99m 99m 99m 99m99m



99m 3 +


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99m


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99m




188


188



2 2




99m 123131


123 131

123 131

X

X

X

X




123 13199m

99m



III


9999m III2

nn III



99m


99m



99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

X






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1






99m99

1



99m


99m 1899m

99m



99m 2 3 3 +




99m


99m

X

X

X

X






99m

hex2 hex

99m

hex



99m


99m99m

99m0 1

99m1 2

99m2 4





X

X

X





33 2 3

+



99m


99m

5099m

99m99m



99m 3


99m

i99m

99m



99m


99m 3+99m

X

X

X

X





99m 3


99m

399m 99m

3



99m 3


18 18

99m99m

3+

99m 99m3



99m 5


99m 99m 99m4

1

599m 99m

410

5

99m 99m99m 99m



99m 99m

X

X

X




99m99m




99m

hex2 hex

99m

hex



99m



199m

99m




X

X

X

X




1 2 3 Next gt




99m


99m 99m 99m6 13

99m99m 99m 99m99m 99m 99m 99m99m



99m 3 +


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2 2 22

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99m




188


188



2 2




99m 123131


123 131

123 131

X

X

X

X




123 13199m

99m



III


9999m III2

nn III



99m


99m



99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

X






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


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642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1






99m

hex2 hex

99m

hex



99m


99m99m

99m0 1

99m1 2

99m2 4





X

X

X





33 2 3

+



99m


99m

5099m

99m99m



99m 3


99m

i99m

99m



99m


99m 3+99m

X

X

X

X





99m 3


99m

399m 99m

3



99m 3


18 18

99m99m

3+

99m 99m3



99m 5


99m 99m 99m4

1

599m 99m

410

5

99m 99m99m 99m



99m 99m

X

X

X




99m99m




99m

hex2 hex

99m

hex



99m



199m

99m




X

X

X

X




1 2 3 Next gt




99m


99m 99m 99m6 13

99m99m 99m 99m99m 99m 99m 99m99m



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188



2 2




99m 123131


123 131

123 131

X

X

X

X




123 13199m

99m



III


9999m III2

nn III



99m


99m



99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

X






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












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642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1





33 2 3

+



99m


99m

5099m

99m99m



99m 3


99m

i99m

99m



99m


99m 3+99m

X

X

X

X





99m 3


99m

399m 99m

3



99m 3


18 18

99m99m

3+

99m 99m3



99m 5


99m 99m 99m4

1

599m 99m

410

5

99m 99m99m 99m



99m 99m

X

X

X




99m99m




99m

hex2 hex

99m

hex



99m



199m

99m




X

X

X

X




1 2 3 Next gt




99m


99m 99m 99m6 13

99m99m 99m 99m99m 99m 99m 99m99m



99m 3 +


99m

2 2 22

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99m 186 188

99m3

3 99m99m 99m

99m


X





99m




188


188



2 2




99m 123131


123 131

123 131

X

X

X

X




123 13199m

99m



III


9999m III2

nn III



99m


99m



99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

X






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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1015 15 15 15

111


X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1





99m 3


99m

399m 99m

3



99m 3


18 18

99m99m

3+

99m 99m3



99m 5


99m 99m 99m4

1

599m 99m

410

5

99m 99m99m 99m



99m 99m

X

X

X




99m99m




99m

hex2 hex

99m

hex



99m



199m

99m




X

X

X

X




1 2 3 Next gt




99m


99m 99m 99m6 13

99m99m 99m 99m99m 99m 99m 99m99m



99m 3 +


99m

2 2 22

X

X



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99m3

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99m


X





99m




188


188



2 2




99m 123131


123 131

123 131

X

X

X

X




123 13199m

99m



III


9999m III2

nn III



99m


99m



99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

X






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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111


X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1




99m99m




99m

hex2 hex

99m

hex



99m



199m

99m




X

X

X

X




1 2 3 Next gt




99m


99m 99m 99m6 13

99m99m 99m 99m99m 99m 99m 99m99m



99m 3 +


99m

2 2 22

X

X



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99m3

3 99m99m 99m

99m


X





99m




188


188



2 2




99m 123131


123 131

123 131

X

X

X

X




123 13199m

99m



III


9999m III2

nn III



99m


99m



99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

X






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1




1 2 3 Next gt




99m


99m 99m 99m6 13

99m99m 99m 99m99m 99m 99m 99m99m



99m 3 +


99m

2 2 22

X

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99m3

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99m


X





99m




188


188



2 2




99m 123131


123 131

123 131

X

X

X

X




123 13199m

99m



III


9999m III2

nn III



99m


99m



99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

X






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




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99m


X





99m




188


188



2 2




99m 123131


123 131

123 131

X

X

X

X




123 13199m

99m



III


9999m III2

nn III



99m


99m



99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

X






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1





99m




188


188



2 2




99m 123131


123 131

123 131

X

X

X

X




123 13199m

99m



III


9999m III2

nn III



99m


99m



99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

X






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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1015 15 15 15

111


X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1




123 13199m

99m



III


9999m III2

nn III



99m


99m



99m 3 +


1 23

21

99m3

+

4 2 3 3 2 3


99m 3 +

X

X

X






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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111


X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1






1 23

minus 299m

2 34 2 3 3 2

1



3 99m


399m

3



99m 2


99m2

4 2 3 32 3

3



2 2 3


3+

X

X

X

X




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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111


X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1




3 2 2 3

4 2 3 3 23

3



99m 2 3


99m3

+ 99m2

3

32 3

3





99m 99m99m 99m




99m 11

99m 11

3410 7 11 11

X

X

X




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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1015 15 15 15

111


X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1




3410 7 113ndash13

1111



99m


99m

99m 99m






99m


99m99m

299m


99m

X

X

X







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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111


X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1







89


8989

8989 4+ 89 4+ 89 4+




68

68

v 3




X

X

X

X




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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111


X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1




11 18 64 86



64 v 3



6412

+ minus64







24 minus1 minus1

1212


X

X

X







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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1015 15 15 15

111


X






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1







44m 44



44 +12

47 minus12

6864 177 90 44 44m

1244 44m 44 68 111

90 177




676868 68 68

4 22 1 2 3 2 2 2 4




225 213 211

X

X

X

X




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1




225 213 211

2 2225 211








4 2 23+

682

2 2



45


45

45


X

X

X



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1



p632




68 68

6971




II 6464 67



64




2 2 64


64

2 2

2 2

X

X

X

X








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1








141


141frac12

141β(max)

γ140 141

3 4140 14 2

143140




8989

89

89


64

64

X

X

X





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



MobileRSS Feeds


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64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1





64


d



nat6768


68

68 3+3+



4 4


4 44 4

3+ 3+4

4




X

X

X

X




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



MobileRSS Feeds


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64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1




ihigh high



64


6464




64



64




X

X

X

X












68


68

X

X



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64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1












68


68

X

X



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64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




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642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1






2

2



68




64 2



642

642



47


4712

minus minusav

X

X

X

X





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1





89





188 188



177





v 3

642

64

X

X

X

X





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1





2

642

nat2



89


8989

89




frac12




8612

+avg

8664

X

X

X





67


6767

673

3+



68



18 99m68

68 3+68 68





X

X

X






111



68 2



68

2

68

683




125

125 177


64

X

X

X



p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

X





177




11 11


116 13

11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

90





X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

99m



67


12

6467



4344g 45


4344g 45




15 minus2 minus1

X

X

X

X




15 minus2 minus1

minusmax

12



99m


99 99m






99 99m


99m nat3

99m99m

99m



57


57

X

X

X

X




57



99m 100


99m 100 99m

99m



99m


99m





X

X

X




lt Prev 1 2 3




X


Slide Number 1





67


6767

673

3+



68



18 99m68

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125

125 177


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p642ndash643



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17 1899

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1617 1618 9916

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2minus 16

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68




64


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177

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68 99m

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186 99m


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1003

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6467



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15 minus2 minus1

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p642ndash643



99m64




17 1899

4 499

1617 1618 9916

217

2minus 16

318 minus 16

317 minus 16

217 18 minus 16

218

2minus

163

18 163




68




64


64

177

X

X

X

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177




11 11


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11 11 11111




v 32




68 99m

89

X

X

X

X





89








111 68

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X

X

X

X






197m12 γ

19712 γ



52g 147




44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

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99m


99m 99

99m



67


12

6467



4344g 45


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15 minus2 minus1

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15 minus2 minus1

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p642ndash643



99m64




17 1899

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68




64


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177

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177




11 11


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11 11 11111




v 32




68 99m

89

X

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X

X

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197m12 γ

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44 44


4468

1290 177 44

44 4444 44 44



186 99m


99m 18699m

186100 186 100

1003

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X

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15 minus2 minus1

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197m12 γ

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44 44


4468

1290 177 44

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186 99m


99m 18699m

186100 186 100

1003

1863

X

X

X

X






99m


99m 99

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67


12

6467



4344g 45


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186 99m


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186100 186 100

1003

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X

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2014 terachem-nuclear medicine and biology, v. 41, is. 7, p. 547-650

Education

Transcript of 2014 terachem-nuclear medicine and biology, v. 41, is. 7, p. 547-650