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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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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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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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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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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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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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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.