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Life Analytical Chemistry-Molecular Imaging (MI): Nuclear Imaging

Gaolin Liang （梁高林） , Ph. D.Professor, Ph. D. AdvisorDeptartment of Chemistry

University of Science and Technology of China

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“ 异域秋分暑未休 平居四载有乡愁 人生岂尽如心事 更忆霜白叶落秋”

By Wei Huang, Ph.D. candidate Stanford University

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“ 孤身疾影下庐阳 报国为家意欲畅 舒拳展腿犹未达 纷花乱眼仍断肠”

By Gaolin Liang, Professor USTC

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Nuclear Imaging

PET

SPECT

Fusion techniques: PET/CT

Fusion techniques: SPECT/CT

Practical concerns in nuclear imagingThe amount of radiation from diagnostic nuclear medicine procedures is kept within a safe limit and follows the "ALARA" (As Low As Reasonably Achievable) principle.

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PET 的名字来源于：Positron ，正电子，Emission ，发射，Tomography ，断层摄影术。

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Using 18F,11C,15O, 64Cu…for PET imaging

Oxygen (15O, T1/2 = 2 min); nitrogen (13N, T1/2 = 10 min); carbon (11C, T1/2 = 20 min); fluorine (18F, T1/2 = 110 min), copper (64Cu, T1/2 = 12 h) and iodine (124I, T1/2 = 4 days).

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[18F]-fluoro-deoxy-glucose

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Physiologic distribution of [18F]-FDG

After i.v. injection, [18F]-FDG is distributed in the body likeglucose. In accord with the glucose consumption of the cells,it is taken up by the glucose transport proteins, mainly bythe GLUT-I, and phosphorylyzed by the hexokinase. Unlikeglucose, [18F]-FDG does not take part in further steps ofthe glucose metabolism, which leads to a trapping of themolecule in the cells. Due to increased anaerobic glycolysis,many tumor cells show an up regulation of GLUT-I and ofhexokinase, which together with physiologic trapping leadsto an accumulation of FDG.

[18F]-FDG is mainly excreted by the kidneys.

In normal tissues, [18F]-FDG does not show a uniform distribution.The most intense physiologic uptake is seen inbrain tissue, which is diagnostically used for a wide rangeof indications in neurology and psychiatry.

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[18F]-FDG- HEAD AND NECK

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[18F]-FDG- MYOCARDIUM

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[18F]-FDG- GASTROINTESTINAL TRACT

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[18F]-FDG- GENITOURINARY

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[18F]-FDG- MUSCULAR ACTIVITY

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[18F]-FDG- THYMUS UPTAKE

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[18F]-FDG- BONE MARROW

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[18F]-FDG- SPLENIC UPTAKE

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[18F]-FDG- BENIGN PATHOLOGIC CAUSES OF 18F-FDG UPTAKE

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Probes, applications, and instrumentations

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NOTf

COOEt

18F-

18F

COOEt

18F

COOH

1. NaOH2. HCl

Bu4NOH, CH3CN

NO O

O

Me2N

NMe2BF4

TSTU

18F

C

O

N

O

O

O

CO NH

HNHN

NH

OO

O

NHO

HO

ONH

NH2

NH

NH

HOOCHN

NHNH

HN

OO

O

HNO

OH

ONH

H2N

NH

OHNH

O

NH2

O

CO NH

HNHN

NH

OO

O

NHO

HO

ONH

NH2

NH

NH

HOOCHN

NHNH

HN

OO

O

HNO

OH

ONH

H2N

NH

OHNH

O

HN

O

O

F18

[18F]-FB [18F]-SFB

pH 8.0 in aqueous buffer or DIPEA in DMSO

[18F]FRGD2

18F-SFB Synthesis

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• 1 mL K222/K2CO3 (15 mg/ml & 3 mg/ml in 9:1 ACN/H2O)• drying• 4-5 mg precursor, 1 ml anhydrous DMSO, 120 °C for 20 min• Add 10 mL H2O, C18 cartridge, wash once with 5 mL H2O• 3 mL ACN (with 50 μL Bu4NOH) to rinse the cartridge• 20 mg TSTU, 90 °C for 10 min• HPLC purify, Rt: 23.4-24.4 min (7-37min: 5 – 65 % ACN)• C18 cartridge, wash it once (5 mL H2O)• 1 mL ACN rinse the cartridge (18F-SFB)

• Typical peptide labeling (Lys side chain): 10 mCi 18F-SFB + 0.4 mg peptide Total time: 1 h Decay-corrected yield: 30-60% (5-10 peptides)

• Typical protein labeling (Lys side chain): 10 mCi 18F-SFB + 0.4 mg protein Total time: 30-40 min Decay-corrected yield: 1-30% (3-5 proteins)

Procedure

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HN

HN

NH

HN

O

O

O

O

HN

O

HN

H2N

NH

NH2HN

H2N NH

NH

S

O

S

NH

S

NCNH

N

HN

O

NH

18F

O

Liang, G.L.; et al. Unpublished results.

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Xiaoyuan (Shawn) Chen, Ph.D.

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

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Single Photon Emission Computed Tomography (SPECT)

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Study Radioisotope

Emission energy (keV)

Half-lifeRadiopharmaceutical

Activity (MBq)

Rotation (degrees)

Projections

Image resolution

Time per projection (s)

Bone scantechnetium-99m

140 6 hours

Phosphonates / Bisphosphonates

800 360 120 128 x 128 30

Myocardial perfusion scan

technetium-99m

140 6 hourstetrofosmin; Sestamibi

700 180 60 64 x 64 25

Brain scantechnetium-99m

140 6 hoursHMPAO; ECD

555-1110

360 64 128 x 128 30

Tumor scan

iodine-123 159 13 hours MIBG 400 360 60 64 x 64 30

White cell scan

indium-111 & technetium-99m

171 & 245

67 hoursin vitro labelled leucocytes

18 360 60 64 x 64 30

Wikipedia

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Structures of Tc-99m probes

MDPSestamibi

ECD

BZM

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SPECT/CT

S

NCN

NH

O

OH125I

HN

ONH

SS

O

NH

NH2HN

HN

O

HN

H2N NH

NH

OHN

OHN

HN

H2NNH

O

furin

S

NCN

NH

O

OH125I

HN

OH2N

HS

S

N

NH

O

OH125I

HN

OH2N

HS

S

NCN

NH

O

OH125I

HN

OS

N

n

Reduction

Condensation

Self-assemble

Nps

Qingqing Miao, Xiaoyu Bai, Yingying Shen, Bin Mei, Jinhao Gao, Li Li, and Gaolin Liang*. Intracellular self-assembly of nanoparticles for enhancing cell uptake. Chemical Communications. 2012, 48 (78), 9738-9740.

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SPECT/CT

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SPECT/CT FOR SLN MAPPING

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SPECT/CT IN SKELETAL DISEASES- Applications in Malignant Skeletal Diseases

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SPECT/CT IN DIFFERENTIATED THYROID CANCER

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SPECT/CT IN PARATHYROID TUMORS

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SPECT/CT IN TUMORS OF SYMPATHETIC NERVOUSSYSTEM AND ADRENOCORTICAL TUMORS

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