Technetium & Rhenium Chemistry - chem.uzh.cha16b0736-3211-4b17-b067-aa5016348a89/... · Technetium...

Technetium & Rhenium Chemistry

1

Radionuclides for Radiopharmacy

Requirements for molecular imaging

The three most important properties of the radionuclide

Can we take any radionuclide for imaging or therapy ?

the radiation dose to the patient

penetration of tissue (Eg > 80 keV)

efficiency of detection

half-life

type of radiation emitted

energy of radiation emitted


2



Half-life

Should be long enough to complete the scan, short enough that

the activity in the patient decreases rapidly after the scan.

Typically in the range of few hours.

The dose might be kept as low as possible (achievable)


3


pure g-ray emitting nuclides are preferred since

Diagnosis

Therapy

a and b- radiation (particles) and g-ray emitters

are preferred


Type of radiation emitted


4



Energy of g-radiation for imaging with SPECT

Should be greater than approx. 80 keV, g-rays can penetrate tissue

Should be less than approx. 300 keV, the g-rays can be detected and

collimated

Specific activity

Should be as high as possible. Only trace amounts of pharmaceutical (or stable element) need to be administered.


5



Further considerations

Toxicity

Availability

Costs

132.9

Cs55

137.3

Ba56

Fr87

Ra88

138.9

La57

178.5

Hf72

180.9

Ta73

183.8

W74

186.2

Re75

190.2

Os76

Ac89

Rf104

Db105

Sg106

Bh107

Hs108

192.2

Ir77

195.1

Pt78

197.0

Au79

200.6

Hg80

Mt109

Ds110

Rg111

Cn112

1.01

H1

4.00

He2

6.97

Li3

9.01

Be4

22.99

Na11

10.81

B5

12.01

C6

14.00

N7

15.99

O8

19.00

F9

20.18

Ne10

24.30

Mg12

26.98

Al13

28.08

Si14

30.97

P15

32.07

S16

32.45

Cl17

39.95

Ar18

39.10

K19

40.08

Ca20

69.72

Ga31

72.63

Ge32

74.92

As33

78.97

Se34

79.91

Br35

83.80

Kr36

85.47

Rb37

87.62

Sr38

44.96

Sc21

47.87

Ti22

50.94

V23

52.00

Cr24

54.94

Mn25

55.85

Fe26

88.91

Y39

91.22

Zr40

92.91

Nb41

95.95

Mo42

Tc43

101.1

Ru44

58.93

Co27

58.69

Ni28

63.55

Cu29

65.38

Zn30

102.9

Rh45

106.4

Pd46

107.9

Ag47

112.4

Cd48

114.8

In49

118.7

Sn50

121.8

Sb51

127.6

Te52

126.9

I53

131.3

Xe54

204.4

Tl81

207.2

Pb82

209.0

Bi83

Po84

At85

Rn86

Nh113

Fl114

Mc115

Lv116

Ts117

Og118

140.1

Ce58

140.9

Pr59

232.0

Th90

231.0

Pa91

144.2

Nd60

Pm61

150.4

Sm62

152.0

Eu63

157.3

Gd64

158.9

Tb65

238.0

U92

Np93

Pu94

Am95

Cm96

Bk97

162.5

Dy66

164.9

Ho67

167.3

Er68

168.9

Tm69

Cf98

Es99

Fm100

Md101

173.0

Yb70

175.0

Lu71

No102

Lr103

57-71

89-103

b– therapy g imaging

b+ imaging

a therapy

mixed

1

2

3 64 5 7 108 9 11 12

13 14 15 16 17

18


6

Elements with suitable isotopes for nuclear medical applications


7

Rhenium

Re: 1925 discovered by Ida Noddack as the last unknown, stable element

186Re: t1/2 = 3.72 d, b- (93.1%) + EC (6.9%), Emax = 1.07 MeV

Generator

Reactor / Cyclotron

188Re: t1/2 = 17 h, b- (100%), Emax = 2.12 MeV


8

Technetium

Tc: 1937 discovered from a nuclear reaction by Perrier and Segré

98Mo 95mTc(d,n)

96Mo 97mTc(d,n)


9

Technetium

H. Braband, CHIMIA, 2011,65, 776.

http://de.wikipedia.org/wiki/Sellafieldhttp://de.wikipedia.org/wiki/Kernkraftwerk_Leibstadtb- – emitter

Emax = 0.29 MeV

T1/2 = 2.1· 105 a

Fission product in nuclear power plants

Estimated 99Tc production per year = 3000 kg


10

Technetium

http://de.wikipedia.org/wiki/Sellafieldhttp://de.wikipedia.org/wiki/Kernkraftwerk_Leibstadt

http://chartingprogress.defra.gov.uk/clean-seas-radioactivity#fig1

Distribution of 99Tc in Irish Sea (2005 / 2006)

b- – emitter

Emax = 0.29 MeV

T1/2 = 2.1· 105 a




11

99-Technetium, how to handle?

Analytical Methods:

IR, NMR, X-ray, UV,

HPLC, LSC (99Tc EA), „MS“

b- – emitter

Emax = 0.29 MeV

T1/2 = 2.1· 105 a




12

Single-Photon Emission Computed Tomography

g - emitter

E = 140 keV

T1/2 = 6 h

Generator nuclide

c([99mTcO4]-) ≈ 10-6 - 10-9 mol/l

Myocardial Perfusionwww.uk-erlangen.de


13

The matched pair

Enables the combination of diagnostic and therapy at the

same molecular scaffold (“Theranostics”)

132.9

Cs55

137.3

Ba56

Fr87

Ra88

178.5

Hf72

180.9

Ta73

183.8

W74

186.2

Re75

190.2

Os76

Rf104

Db105

Sg106

Bh107

Hs108

192.2

Ir77

195.1

Pt78

197.0

Au79

200.6

Hg80

Mt109

Ds110

Rg111

Cn112

1.01

H1

4.00

He2

6.97

Li3

9.01

Be4

22.99

Na11

10.81

B5

12.01

C6

14.00

N7

15.99

O8

19.00

F9

20.18

Ne10

24.30

Mg12

26.98

Al13

28.08

Si14

30.97

P15

32.07

S16

32.45

Cl17

39.95

Ar18

39.10

K19

40.08

Ca20

69.72

Ga31

72.63

Ge32

74.92

As33

78.97

Se34

79.91

Br35

83.80

Kr36

85.47

Rb37

87.62

Sr38

44.96

Sc21

47.87

Ti22

50.94

V23

52.00

Cr24

54.94

Mn25

55.85

Fe26

88.91

Y39

91.22

Zr40

92.91

Nb41

95.95

Mo42

Tc43

101.1

Ru44

58.93

Co27

58.69

Ni28

63.55

Cu29

65.38

Zn30

102.9

Rh45

106.4

Pd46

107.9

Ag47

112.4

Cd48

114.8

In49

118.7

Sn50

121.8

Sb51

127.6

Te52

126.9

I53

131.3

Xe54

204.4

Tl81

207.2

Pb82

209.0

Bi83

Po84

At85

Rn86

Nh113

Fl114

Mc115

Lv116

Ts117

Og118

57-71

89-103

b– therapy g imaging

b+ imaging

a therapy

mixed

1

2

3 64 5 7 108 9 11 12

13 14 15 16 17

18


14

Similarities - Differences

Starting materials: [TcO4]- and [ReO4]

- are structurally very similar

Re-O 1.690 Å (av)Tc-O 1.670 Å (av)

Both elements exist in oxidation states from –III to +VII


15


Electrochemistry

[TcO4]- [TcO4]2- [TcO2] Tc+0.27

+0.74

+0.63

+0.47

VII VI IV 0

+0.81

[MnO4]- [MnO4]2- [MnO2] Mn+0.32

+1.69

+0.9

+0.91

+1.28

[ReO4]- [ReO2] Re+0.28

+0.52

+0.72

+0.42

+0.4[ReO3]

Large difference Mn Tc

Small difference Tc Re


16


Re is easier reoxidized than Tc

ReV compounds are often unstable against air (in radiopharmacy)

[ReO4]- is more difficult to reduce than [TcO4]

-

stronger reducing agents and/or longer reaction times are required

The [99mTc(OH2)(CO)3]+ is easily achieved for 99mTc but requires harsh

conditions for [188Re(OH2)(CO)3]+

Consequences

The HYNIC approach is very convenient for 99mTc but does not work for 188Re


17

Coordination Chemistry

Tc and Re have a rich coordination chemistry (in water)

Large diversity of complexes, in contrast to radioisotopes

of the „3+ family“ (68Ga3+, 111In3+, 89/90Y3+, 153Sm3+, 177Lu3+)

Known oxidation states from -III to +VII

Most stable oxidation state + VII, +IV

The most important oxidation states +VII, +V, and +I

Only stable and readily accessible oxidation states are of interest

Stable oxidation states are often characterized by chemically

robust core structures

{MVIIO3}+, {MVO}3+,{MVO2}

+, {MVN}2+, {MI(CO)3}+ M = Tc, Re


18

Coordination Chemistry

tetrahedral quadratic

pyramidal

trigonal

bipyramidal

octahedral

Members of the „3+ family“ exclusively prefer the coordination number 6

→ macrocyclic ligand systems (e.g. DOTA)

In contrast


19

Relevant oxidation states and core structures

[Tc(V)]3+ [Tc(V)]+ [Tc(V)] ?

HYNIC

[Tc(V)]2+

[Tc(I)]+[Tc(III)]+


20

The {TcO}3+ core

Most extensively studied Tc metal core for radiopharmaceutical applications

Contains Tc at the oxidation state +V (d2 system)

Square pyramidal coordination geometry with a strong p-bonding oxo-

group in the apical position

Is stabilized by s- and p-donating amino, amido, and thiolate ligands


21

The {TcO}3+ core

+ Sn2+,

glyco heptonate

(auxiliary ligand)

(TBA)[99TcO4] + conc. HCl

99Tc

{99mTcO(gh)2}

99mTc

[99mTcO4]-

+ MAG3

Precursor for 99TcV chemistry


22

The {TcO}3+ core

Perfusion tracer:

Neurolite® Ceretec®

brain

99mTc-MAG3

Technescan®

99mTc-EC

renal


23

The {TcO2}+ core

Strong s-donating ligands and basic conditions lead to a fast

transformation of the {TcO}3+ core into the {TcO2}+ core

+ H2O

- H2O

- H+

+ H+

- H+

+ H+

Reduction of electron density at the metal centre


24

The {TcO2}+ core

Perfusion tracer:

heart

99mTc-Tetrofosmin

Myoview®

bone


25

The {TcN}2+ core

Square pyramidal coordination geometry with a strong p-bonding oxo-

group in the apical position

Superior redox stability (compared to the {TcO}3+ core), due to the

stronger p-donating properties of the N ligand

Contains Tc at the oxidation state +V (d2 system)

Is stabilized by the same s- and p-donating ligands as the {TcO}3+ core

Especially, complexes with (bis)thiocarbamato and PXP

bisphosphane ligands showed good in vivo stability


26

The {TcN}2+ core

r.t., 30 min

EtOH / H2O

+ 1 mg PNP

(NH4)[99TcO4] + NaN3 + conc. HCl

+ PR3

(NH4)[99mTcO4]

+ 5 mg SDH (hydrazide),

Sn(II)

r.t., 10 - 15 min{99mTc N}

labeling

50°C, 60 min

99Tc

99mTc

Duatti et al., Bioconjugate Chem. 2004, 15, 628.


27

The {TcN}2+ core

Perfusion tracer:

heart

99mTc-DBODC5 99mTc-NOET

brain


28

The {Tc(HYNIC)} core

Metal-oxo species react with hydrazine groups (condensation reaction)

HYNIC (hydrazinonicotinic acid) has been established for the labeling

of peptides, proteins, and antibodies

Blower et al., Inorg. Chim. Acta, 2010, 363, 1059.


29



++ coligand L

or

(assumed structure)


30



Problem

The coordination mode (mono- or bidentate) of the HYNIC ligand is hard

to distinguish and is highly dependent on the reaction conditions and the

coligands L

The oxidation state of the metal atom is not defined

The value of HYNIC as a BFC for 186/188Re remains unproven

Structural modes adopted by

pyridylhydrazine in its coordination

chemistry


31

The fac-{TcCO3}+ core

The d6 low-spin system is very stable

Exists without stabilizing ligands ([99mTc(OH2)(CO)3]+)

The solvato molecules can be replaced by a wide range of ligand

systems (tridentate ligands are most versatile)

In general, complexes are highly robust and do not decompose

in serum or in vivo

The coordination chemistry is in many cases identical to the Re homolog

Octahedral geometry, facial coordinated CO groups


32


[99mTcO4]-

Na2[H3BCO2] /

water, 15 min, 90 °C

[99TcO4]-

1. BH3∙THF, 1 atm CO, 5h, RT

2. HCl, TEACl, EtOH

99Tc

99mTc


33


The [99(m)Tc(CO)3]+ core accepts

very different ligand types

papc types

aromatic amines

agostic hydrides

cyclopentadienyls

histidine type

polyamines

hard soft


34

Application of 99mTc in nuclear medicine

Every 3rd patient in the USA receiving stationary treatment

receives a scintigram or SPECT

Study indication

Aspiration study Cardiac, Resting RNV Liver-Spleen scan Renal, Tubular Agents

Bone, Skeletal imaging Cardiac, R to L Shunt Lung, Perfusion (1st) Renal, cystogram

Bone Marrow imaging Gallbladder Ejection Fraction Lung, Ventilation (2nd) Salivary imaging

Brain, PerfusionGastric Emptying, Liquid

PhaseLymphoscintigraphy Spleen imaging

Brain, Shunt Patency Gastric, Reflux study Meckel's scan Testicular

Cardiac, Perfusion GI Bleeding Parathyroid imaging Therapy, P. Vera

Cardiac, Infarct imaging Hepatobiliary Renal, Cortical agents Therapy, Thyroid

Cardiac, Exercise RNV Hemangioma study Renal, Cortical agents Thyroid, Scan

Cardiac, First Pass RNV Infection Renal, Glomerular agents Tumor imaging

20 Mio. nuclear medical studies per year; > 70 % with 99mTc!


35


Molybdenum and technetium are chemically different and can be separated

Generator System

[99MoO4]2- [99mTcO4]

-

[99MoO4]2- is loaded on

the Al2O3 column

[99mTcO4]- is eluted from

the Al2O3 column


36


The available activity decays according to

A = A0•(2n) n = number of half life times


37


Activity of 99Mo in a typical hospital generator: 13 GBq

elution after 99mTc [M] amount99mTc [ng]

amount99Tc [ng]

ratio activity

[GBq]

4 h 0.0610-6 39 47 1:1 4.77

12 h 0.1310-6 79 139 1:2 10.58

24 h 0.1710-6 98 288 1:3 13

A =N

t1/2

These little amounts will have consequences for chemistry


38


The first generator produced

at Brookhaven Nat. Lab.

Modern designs


39

The “Technetium Issue” / 99Mo shortage

40%

30%

10%

9%3%

Reactors used by large-scale producers of 99Mo and % of worldwide production

National Research Universal(NRU), Chalk River, Canada(1957, will be shut down in 2016)

High Flux Reactor (HFR), Petten,Netherlands (1961)

South Africa Fundamental AtomicReactor Installation-1 (SAFARI-1),South Africa (1965)

Belgium Reactor-2 (Br2), Belgium(1961)

OSIRIS, France (1966)

G. S. Thomas, J. Maddahi; J. Nucl. Cardiol., 2010, 17, 993.


40

Preparation of Tc & Re Radioprobes

Addition of

[99mTcO4]- to

kit vial

Final productAspiration of

[99mTcO4]-


41

Preparation

Characteristics

This makes chemistry with transition metals rather challenging!


For 99mTc radioprobes, kit formulation is a crucial point (one pot reactions)

Requirements:synthesis fully in aqueous solution

yield > 98%, injectable

time < 30 min

high specific activity

metabolically stable or controlled metabolism

fast excretion from non-target organs

organ specificity

Novel synthetic approaches (techniques) are possible but have

to compete with modern PET tracers (practical & economical)


42


In presence of an (auxiliary) ligand:

Key step: Reduction of [MO4]- (M = 99mTc, 186/188Re)

Exception: The [99mTc(OH2)(CO)3]+ exists without stabilizing ligands

In absence of an (auxiliary) ligand:

99mTcVIIO4- + SnII + auxiliary ligand

SnIVO2 + 99mTcred- auxiliary ligand

99mTcred- Ligand + auxiliary ligand

99mTcVIIO4- + SnII → SnIVO2 + 99mTcO2 (colloidale pertechnetate)


43


In general

desired

product

99mTcVIIO4- + SnIICl2 + auxiliary ligand SnIVO2 + [99mTcred-aux. ligand]

Ligand, L

99mTcIVO2

in general

undesired side

product

[99mTcred- Ligand] + auxiliary ligand

Exception: The [99mTc(OH2)(CO)3]+ exists without stabilizing ligands


44


General Composition of a 99mTc-Labeling Kit

Active component/ligand (forms a thermodynamically stable, reduced 99mTc-

complex), e.g. HMPAO, MIBI, MDP...

Reducing agent, e.g. SnCl2

Auxiliary components

Antioxidant (prevents pre-mature oxidation of Sn+II to Sn+IV )

e.g. Ascorbic acid

Buffer salt and other salts

e.g. NaCl

Other auxiliary component (for lyophilisation of the kit)

e.g. Mannitol, Lactose

Auxiliary ligand (forms a kinetically stable, reduced, intermediate 99mTc-complex),

e.g. Sodium-gluconate, -citrate, -tartrate


45


Example: 99mTc-Sestamibi Kit

Ligand (only MIBI)

Reducing agent

Aux. ligand I

Aux. ligand II

Aux. component


46


Blood flow in the heart muscle at rest and

during stress

The heart scan, from a patient with coronary artery disease, shows where the heart

muscle lacks adequate blood flow.

Example: 99mTc-Sestamibi Kit


47


The bone scan is from a patient with prostate cancer that

has spread to the spine and other bones.

The radiopharmaceutical, similar to the mineral in bone,

accumulates at bone tumors (dark spots) because the

diseased bone has faster mineral turnover.

Detection of small metastasis in bones

[99mTc-mdp]: unknown structure

Medronic acid

Example: 99mTc-MDP Kit


48


Example for a “matched pair” application

Detection of small metastasis in bones

[99mTcO(dmsa)2](n-)

Tc

Injection

600 MBq

Diagnosis

dmsa = dimer captosuccinic acid

Blower, P. J.; et al Eur. J. Nucl. Med. 2000, 27, 1405-1409.


49


Example for a “matched pair” application

Treatment of small metastasis in bones

b: 100%, 2.1 MeV

therapy by “cross fire effect”

[188ReO(dmsa)2](n-)

Injection

370 MBq

Therapy


50

Radioprobe development – a multidimensional project


51

Radioprobe development – a multidimensional project

Science

(Visions, Options)

User

(Reality, Needs)

The common communication problem


52

Labelling strategies

Radiolabeling via covalent bonds: Radiolabeling via coordinative bonds:

direct radiolabeling

+

indirect radiolabeling

«organic» or halogen

radionuclides

radiometals

Fludeoxyglucose ([18F]FDG)


53


The general synthetic strategy in 99mTc / 186/188Re radiopharmacy

are building blocks

Building blocks (cores) are complexes or fragments which can be:

incorporated into a bifunctional chelator pendent to a biomolecule

or directly be coordinated to a biomolecule of interest

or both, in one step but via in situ prepared building block

[99mTcO4]-

OH2

Tc

CO

OC CO

OH2H2O

Biomolecule with

pendent BFC

with in situ building block


54


Perfusion radiotracer (1. Generation): Target specific radio tracer (2. Generation):

99mTc-Sestamibi

Cardiolite ®

Radioconjugates of a chemical inert

metal complex and a target specific

biomolecule


55


Direct Labeling Bifunctional Chelator Concept

Progesteron

Biomimetic Approach

A large diversity of bifunctional

coupling agents for labeling of

biomolecules have been developed


56

Bifunctional Chelator Concept

prostate-specific membrane antigene

inhibitor (PSMA)

Zubieta et al., Nucl. Med. Biol., 2005, 32, 1.

Liu, Asv. Drug Delivery Rev. 2008, 60, 1347.


57

Single Amino Acid Chelates SAAC

Single Amino Acid Chelates SAAC

HPLC UV trace Re-complex

HPLC g trace 99mTc complex

Zubieta et al., Chem. Commun. 2009, 493.

Valliant et al., J. Am. Chem. Soc. 2004, 126, 8598.


58

Direct Labeling

No (bifunctional) chelator necessary

(a special case for radiometal labeling!)

Destabilizing of the protein structure due to cleavage of

disulfide bonds

Loss of biological function due to the coordination of a

metal to the reactive centre of a protein

Very attractive for labeling with [99mTc(OH2)(CO)3]+,

efficient labeling of His groups


59

Direct Labeling

Phosphine reduction of salmon calcitonin and subsequent direct labeling leads to

peptide recyclisation with 99mTcIII but 188ReV complexes

Blower, et al., Bioconjugate Chem. 2005, 16, 939.

Archimandritis, et al., Anticancer Res. 2002, 22, 2125.

Arif, et al., Appl. Radiat. Isot. 2001, 55, 647.


60

Direct Labeling

e.g. antigranulocyte mAb

BW250/183 («besilesomab»),

«sulesomab»


61

Direct Labeling

“Direct” labeling with 99mTcI/186/188ReI using the His-tag strategy

His-tags can be genetically expressed (purification of the protein on a nickel

affinity column)

The His-tag can be considered as a multidentate ligand

30min, 45°C

[99mTc(OH2)(CO)3]+ 99mTc-DARPIN

+ DARPIN

This gentle procedure allows the radiolabeling of recombinant proteins

"from the shelf", without any chemical modification of the protein

structure

Schubiger et al., Nat. Biotechnol., 1999, 17, 897.


62

Novel labelling strategies

Mindt et al., J Am Chem Soc. 2006,128,15096.

Struthers et al., Chemistry . Eur. J. 2008,14, 6173.

Mindt et al., ChemMedChem. 2010, 5, 2026.

“Click-to-Chelate” strategy

Ligand centered labeling strategy


63


Labeling via (3+2) cycloaddition of fac-{99mTcO3}+ complexes with alkenes

+ alkene

(3+2) cycloaddition

+

Davison et al., Polyhedron, 1988, 7, 1981.

Metal centered labeling strategy


64


[99mTcO4]-, NaOH

Purity >99%

Yield ≈ 80%

Microwave heating (10 min, 110°C): Purity > 99%

Yield ≈ 75%

3.40

+

95°C, 1h, N2,

pH 7∙ 3HCl

Alberto et al., Chem. Commun. 2014, 50, 4126.



65


Alberto et al., Chem. Eur. J. 2011,17,12967.

+

Pharmacophores

+

30 min,

60°C

Amino Acids

+

2 h, 60°C

Carbohydrates

2 h, 40°C



66


++



67


stereo selective!

+

Braband et al., Dalton Trans. 2014, 43, 4260.



68


Alberto et al., Inorg. Chem., 2012, 51, 4051.



69


Development of a target specific nanoplatform, whose bioprofile is

modality independent

Different modalities different bioprofiles

drug

Common Problem for smaller targeting molecules


70


spherical SBA-15

+

Development of a target specific nanoplatform


71


+ [M(CO)3(H2O)3]+

M = Re, 99mTc

M = Re

M = 99mTc

Development of a target specific nanoplatform


72


Extension of the Matched Pair concept (inspired by the biomimetic approach)

99mTc-compounds for imaging – non radio active Re homologues for therapy

lead structure imaging therapy

Rhenium: carbonic anhydrase inhibitors

C. Supuran, Nature 2008, 7, 168.


73


0 5 10 15 20 25 30

0.0

0.2

0.4

0.6

0.8

1.0

Time (min)

Re 99mTc

Ligand

retro-Diels-Alder

reaction



74


Crystallization of CA II with

Alberto et al., Angew. Chem. Int. Ed. 2012, 51, 3354.



75


Extension of the Matched Pair concept by using bisarene complexes

yield: 95%

mono functionalized

bi functionalized

2.5 eq. cysteine

5 eq. K2CO3

H2O / MeOH (1:1)

2.5 eq. cysteine

5 eq. K2CO3

H2O / MeOH (1:1)


76


K[99TcO4] + AlCl3 [99Tc(Me6Ph)(C6H5Br)](PF6)1) hexamethylbenzene (excess)

in bromobenzene, 85°C, 4 h

2) extraction with H2O

3) + NH4PF6



77


[99mTcO4]-

(saline solution)

vacuum

[99mTcO4]- + NaCl (dry)

1) extraction with acetone

2) vacuum

[99mTcO4]- (dry)

+ 10 mg Zn / Al,

10 mg AlCl3,

arene in hexene,

135°C, 60 min

extraction with

saline solution

„The total yield (…) that was isolated

by this procedure varied widley from

day to day and from arene to arene.“

D. W. Wester, et al., J. Med. Chem. 1991, 32, 3284.[99mTc(arene)2]

+

formulation



78


IL coated vial,

[99mTcO4]- (saline solution)

[99mTcO4]- (dry)

+ 100 mg AlCl3,

1 ml arene (liquid)

100°C, 10 min (microwave)

[99mTc(arene)2]+

removing H2OIL = [P(C16H13)3(C14H29)]Br

formulation

yield: > 80% (purity: > 99%)

Extraction with

saline solution

Alberto et al., Chem. Sci., 2015, 6, 165.



79

Take Home Message

Tc and Re have a rich coordination chemistry (in contrast to other radio metals)

Most of the chemical differences between Tc and Re arise from the slightly

different redox potentials

Stable oxidation states are characterized by chemically robust core

structures

Due to the coordination chemistry of Tc and Re, different coordination

geometries can be achieved (in contrasts to members of the „3+ family“)

For most synthesis of 99mTc and 186/188Re radiopharmaceuticals, auxiliary

ligands are necessary to stabilize the metal at the desired oxidation state

A wide range of labeling approaches for 99mTc and 186/188Re have been

developed

Novel strategies use the chemistry of these metals to enable innovative

new possibilities for radioprobe developments

Technetium & Rhenium Chemistry - chem.uzh.cha16b0736-3211-4b17-b067-aa5016348a89/... · Technetium...

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