Life Analytical Chemistry-Molecular Imaging
(MI): Nuclear Imaging
Gaolin Liang （梁高林）, Ph. D.
Professor, Ph. D. Advisor
Deptartment 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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PET Fusion techniques: PET/CT
Nuclear Imaging
SPECT Fusion techniques: SPECT/CT
Practical concerns in nuclear imaging
The 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 like
glucose. In accord with the glucose consumption of the cells,
it is taken up by the glucose transport proteins, mainly by
the GLUT-I, and phosphorylyzed by the hexokinase. Unlike
glucose, [18F]-FDG does not take part in further steps of
the glucose metabolism, which leads to a trapping of the
molecule in the cells. Due to increased anaerobic glycolysis,
many tumor cells show an up regulation of GLUT-I and of
hexokinase, which together with physiologic trapping leads
to an accumulation of FDG.
In normal tissues, [18F]-FDG does not show a uniform distribution.
The most intense physiologic uptake is seen in
brain tissue, which is diagnostically used for a wide range
of indications in neurology and psychiatry.
[18F]-FDG is mainly excreted by the kidneys.
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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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18F-SFB
Synthesis
NMe2
BF4
18
F
Me2N
O
N
O
N
18
O
18
F
F
OTf
1. NaOH
2. HCl
18F-
O
TSTU
C
O
O
Bu4NOH, CH3CN
COOEt
N
COOH
COOEt
O
[18F]-SFB
[18F]-FB
O
O
NH
NH
HO
O
O
NH
O
N
H
HN
HN
NH2
O
O
CO NH
HO
N
H
HN
NH
H2N
NH
HN
O
OH
O
O
O
NH2
O
N
H
NH
O
NH
HO
HN OC
N
H
O
OH
NH
O
O
N
H
HN
HN
O
CO NH
HO
NH
NH2
H2 N
O
O
O
N
H
NH
HN
OH
O
O
O
N
H HN
O
HN
NH
NH
O
HN OC
N
H
OH
pH 8.0 in aqueous buf f er or DIPEA in DMSO
18
F
[18F]FRGD2
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Procedure
•
•
•
•
•
•
•
•
•
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% (35 proteins)
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H2N
NH
H2N
HN
NH
HN
H
N
HN
O
O
O
N
H
H
N
O
S
S
H
N
N
H
O
O
N
O
CN
S
N
H
NH
HN
NH2
O
HN
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F
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
Radioisot
ope
Emissio
n energy Half-life
(keV)
Radiopharm
aceutical
Activit
y
(MBq)
Rotation
(degrees)
Time per
Projection Image
projection
s
resolution
(s)
360
120
128 x 128
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technetium
Bone scan
140
-99m
6 hours
Phosphonate
s/
800
Bisphosphona
tes
Myocardial
technetium
perfusion
140
-99m
scan
6 hours
tetrofosmin;
Sestamibi
700
180
60
64 x 64
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Brain scan
technetium
140
-99m
6 hours
HMPAO; ECD
5551110
360
64
128 x 128
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Tumor
scan
iodine-123 159
13 hours
MIBG
400
360
60
64 x 64
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White cell
scan
indium-111
&
171 &
technetium 245
-99m
67 hours
in vitro
labelled
leucocytes
18
360
60
64 x 64
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Wikipedia
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Structures of Tc-99m probes
BZM
Sestamibi
MDP
ECD
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SPECT/CT
furin
H2N
NH
NH
H2 N
HN
HN
O
H
N
N
H
HN
O
O
H
N
N
O
H
N
N
H
O
O
S
S
N
H
O
NH
HS
H
N
H2 N
N
O
CN
N
H
O
OH
125
I
NH2
HN
CN Reduction
S
S
OH
125
I
Condensation
HS
H
N
H2N
O
N
O
N
H
S
N
H
N
S
O
CN
N n
H
OH
125
I
Self-assemble
N
O
S
Nps
OH
125
I
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 DISEASESApplications 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 NERVOUS
SYSTEM AND ADRENOCORTICAL TUMORS
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