66
INCAPS (IAEA Nuclear CArdiology Protocol Survey)
1. In this survey please include all SPECT Myocardial
Perfusion Imaging studies completed during the
specified week (Monday-Sunday), whether the study
was begun during the specified week or previously.
2. Only include studies in which patients were imaged at
your facility, excluding studies read at your facility but
performed elsewhere.
INCAPS (IAEA Nuclear CArdiology Protocol Survey)
1. In this survey please include all SPECT Myocardial
Perfusion Imaging studies completed during the
specified week (Monday-Sunday), whether the study
was begun during the specified week or previously.
2. Only include studies in which patients were imaged at
your facility, excluding studies read at your facility but
performed elsewhere.
3. Only fill in fields colored green in boxed areas. Lighter
green denotes choose from drop-down menu. Darker
green denotes type-in.
4. Please report data for 1 week period; if less than 25
studies are performed during that week then please
report data for the subsequent week as well.
INCAPS (IAEA Nuclear CArdiology Protocol Survey)
Study
Number Age Sex Weight Technology 1 Technology 2
Example 1 57 M 68 kg
Example 2 82 F 59 kg Transmission source AC
Example 3 65 F 78 kg GE Alcyone technology Prone Imaging
Example 4 64 M 77 kg
CT AC (MDCT –
Multislice CT) Philips Astonish
INCAPS (IAEA Nuclear CArdiology Protocol Survey)
First Injection
Date 1 Activity 1 Units 1 Radiopharmaceutical 1 R/S 1
3-Sep-2012 9.9 mCi Tc-99m sestamibi (Cardiolite®) Rest
4-Sep-2012 3.1 mCi Tl-201 Rest
4-Sep-2012 31.1 mCi Tc-99m tetrofosmin (Myoview®) Stress
5-Sep-2012 10.1 mCi Tc-99m sestamibi (Cardiolite®) Stress
INCAPS (IAEA Nuclear CArdiology Protocol Survey)
Second Injection
Date 2 Activity 2 Units 2 Radiopharmaceutical 2 R/S 2
3-Sep-2012 35.4 mCi Tc-99m sestamibi (Cardiolite®) Stress
4-Sep-2012 28.7 mCi Tc-99m tetrofosmin (Myoview®) Stress
5-Sep-2012 30.5 mCi Tc-99m tetrofosmin (Myoview®) Rest
None
72/M, resting angina, exertional dyspnea, 3-vessel disease on CTCA
40-50%
Rest Low dose DB 3 mo later
LVEF=52%
EDV=111ml
ESV=54ml
LVEF=70%
EDV=93ml
ESV=28ml
LVEF=56%
EDV=103ml
ESV=45ml
Pre-PTCA Post-PTCA
CNUHH, the most beautiful hospital in KOREA
Henry Bom
Department of Nuclear Medicine,
Chonnam National University Hwasun Hospital, Hwasun, Korea
New Experimental Radiotracers
for Myocardial Perfusion
Tc-99m sestamibi
Tc-99m tetrofosmin
Tl-201
Rb-82
Mitochondrium
Uptake of Flow Tracers
Na-K ATPase
Na K
O-15 H2O
free
diffusion
N-13 NH3
carrier
Glutamine
Glutamine synthetase
diffusion
What we need?
SPECT ([99mTc]MIBI) PET ([13N]NH3)
What we need?
• Better image
• Quantitation
• Easy to use
18F perfusion agents
[18F]BMS-747158, Flurpiridaz
Pyridaben
Circulation. 2009, 119: 2333-2342.
Contrast ratios for [13N]NH3
(dashed lines) and
[18F]BMS (solid lines)
measured over 40 minutes.
[18F]BMS-747158, Flurpiridaz
2-Tert-butyl-5-[2-(2-[18F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one
Mitochondrial complex I (MC-I) inhibitor
Bioorganic & Medicinal Chemistry. 2010, 18: 1312–1320
18F perfusion agents
[18
F] FP2OP
Pyridaben
Flurpiridaz
[18
F] FP2OP
Cardiac PET images of a healthy Chinese mini-swine with 85 MBq
[18F]FP2OP in 5% ethanol solution. The images were collected at 5, 15, 30,
60 min after injection, respectively.
18F or 11C18F or 11C
Voltage Sensor : Measurement of
Mitochondrial Membrane Potential
• Rhodamine 123
• Phosphonium salts
P+ 3H
18F perfusion agents
Voltage Sensors
Non-radiolabeled rhodamines are known to accumulate in the
mitochondria in proportion to mitochondrial membrane potential and
are substrates for Pgp, a protein-implicated in multidrug resistance.
Nuclear Medicine and Biology. 2010, 37: 365–370
18F perfusion agents
2-[18
F] fluoroethylrhodamine B
2-[18
F] fluoroethylrhodamine B
MicroPET images of a rat injected with 2-
[18F]fluoroethylrhodamine B.
Time activity curve of a rat myocardium and liver
after injection with 2-[18F]fluoroethylrhodamine B.
18F or 11C18F or 11C
(4-carboxybutyl)
Triphenylphosphonium
Methyltriphenylphosphonium
Tetraphenylphosphonium
Triphenyl
(2pyridylmethyl)phosphonium
tetrabutylphosphonium
P+ COOH P+
P+N
P+ CH3
P+P+ 3H
18F perfusion agents
Phosphonium salts
JJ Min, et al. J Nucl Med. 2004, 45:636–643
P+ 3H
Tetraphenylphosphonium (TPP)
10%
ID/g
0%
2 min 0.5 hr 1 hr 2 hr 4hr
2 min 0.5 hr 1 hr 2 hr 4 hr
Molecular Imaging Program at Stanford (MIPS)
P+ 18F
Cheng Z, et al. J Label Compd Radiopharm. 2005, 48: 131–137
18F perfusion agents
[18F] TPP
Igal Madar, et al. Eur J Nucl Med Mol Imaging. 2007, 34:2057-2065
Igal Madar et al. J Nucl Med. 2006, 47:1359-1366
[18F] fluorobenzyltriphenylphosphonium
18F perfusion agents
[18F] FBnTP
HOX
OH TsOX
OTs TsOX
18Fn n n
+P
R
R
R
P+
R
R
R
X18F
TsOX
18Fn n
[18F]FPTP : X=C, n=1, R=H. Kim et al. J Nucl Med. 2012, 53: 1779-1785
[18F]FHTP : X=C, n=2, R=H. Kim et al. Bioconjugate Chem. 2012, 23(3): 431-437
[18F]FETP : X=O, n=1, R=H. Kim et al. Bioorg. Med. Chem. Lett. 2012, 22: 319–322
[18F]FETMP : X=O, n=1, R=OMe. Kim et al. Nucl Med Biol. 2012, 39: 1093-1098
18F P+ R
Chonnam Style
P+
MicroPET study – [18
F] FPTP
0
2.5
SUV
H
L
H
L
H
L
H
L
1 min 10 min
30 min 60 min
P+18F
[18F]-(fluoropentyl )triphenylphosphonium
J Nucl Med. 2012, 53: 1779-1785
(min)
Ac
tivit
y (
co
un
ts /
pix
el
/ s
ec
)
MicroPET study – [18
F] FPTP
Co
ntr
as
t ra
tio
Time (min)
MicroPET study – [18
F] FPTP
a
Normal
MI model
MicroPET study in Rats – [18
F] FPTP
y = 0.78 x – 3.39
r 2 = 0.92
TT
C (
%)
Polar map (%)
MicroPET study – [18
F] FPTP
2.5
0
S
U
V
[18F]FPTP [13N]NH3
[18
F] FPTP vs. [13
N]NH3
[18F]FPTP TTC
staining 1.0 3.5
[18
F] FPTP vs. [13N]NH3
[13N]NH3
0.6 1.0
Human PET study [18
F] FPTP
[18
F] FHTP
30 min 60 min
0
4
SUV
H
L
H
L
P+
18F
[18F]-labeled (6-fluorohexyl)triphenylphosphonium
[18
F] FETP
0
3.0
SUV
30 min 60 min
H H
L L
P+O
18F
[18F]-labeled (2-(2-fluoroethoxy)ethyl)triphenylphosphonium
[18
F] FETMP
30 min 60 min
H H
L L
P+O
18F
OMe
MeO
OMe
[18F]-labeled (2-(2-fluoroethoxy)ethyl)
tris(4-methoxyphenyl)phosphonium
0
3.0
SUV
SUV
H
L
H
L
H
L
H
L
H
L
H
L
H
L
H
L
MicroPET study
30 min
60 min
[18F]FPTP [18F]FHTP [18F]FETP [18F]FETMP
Take Home Message
• Developed 18F-labeled myocardial perfusion agents target
mitochondria either blocking complex I or being trapped by
electrical charge difference.
Acknowledgments
Laboratory of In Vivo
Molecular Imaging (LOVMI)
Jung-Joon Min, MD, PhD
JiHwa Chong, PhD
Seung-Hwan Park, PhD
Sheng-Nan Jiang, MD
Hyeon-Sik Kim, MS
Vu H. Nguyen, MS
Yoon-Soon Moon, BS
Hyun Hong, BS
Deok-Mi Kim, BS
Dinh V. H. Van
Dongguk University
Laboratory of Instrumental analysis
Kook-Hyun Yu, PhD
Youn-Do Choi, MS
Nuclear Medicine
Hee-Seung Bom, MD, PhD
Ho-Chun Song, MD, PhD
Byeong-Il Lee, PhD
Byung-Hyun Byun, MD
Sun-Pyo Hong, MD
Hwa-Youn Jang, BS
Sang-Min Shin, BS
Stanford University School of Medicine
(Molecular Imaging Program at Stanford)
Sanjiv S. Gambhir, MD, PhD
Zhen Cheng, PhD
Korea Atomic Energy Research Institute
Radiation Biotechnology Research Division
Seung-Dae Yang, PhD
Sang-Wook Kim, PhD
Jeong-Hoon Park, PhD
Hee-Jung Kim, MS
Korea Institute of Radiological and
Medical Sciences (KIRAMS)
Department of Nuclear Medicine
Kyo-Chul Lee, PhD
Sang-Keun Woo, PhD
Chonnam Nat’l University Medical School
Seoul
Chonnam
Bio-Medical Cluster
62Cu-PTSM
N
N
S
N
N
S
H3C
H
62Cu
NH
CH3
N
H
CH3
[62Cu]pyruvaldehyde bis(N4-methylthiosemicarbazone)
• lipophilic, neutral
• FDA approval (Dec 21, 1995)
• Phase I, II, III
J Nucl Med. 1988, 29: 1549-1557
J Nucl Med. 1996, 37: 1294-1300
J Nucl Cardiol. 2001, 8: 67-74.
62Cu-PTSM
68Ga labeling candidates
Lipophilic, cationic complexes
Nuclear Medicine and Biology. 2011, 38: 1165–1174
Nuclear Medicine and Biology. 2009, 36: 39–45
68Ga labeling candidates
Ammonium salt chemical skeleton
Mol Imaging Biol. 2011, 13:128-139
11C-ammonia
11C-ammonia
sestamibi tetrofosmin
99mTc-lipophilic cation
Bioconjugate Chem. 2010, 21: 928–939.
Lipophilic cations
N
N
O
B
O
CH3
O
Cl
O H H
O
99mTc
N
N
NO
N
teboroxime
99mTc-lipophilic, neutral
NOET
Bis[N-ethoxy,N-ethyl(dithiocarbamato)]nitrido Tc (V)
99mTc-calcium channel?
Tc-99m sestamibi
Tc-99m tetrofosmin
Tl-201
Rb-82
Mitochondrium
Uptake of Flow Tracers
Na-K ATPase
Na K
O-15 H2O
free
diffusion
N-13 NH3
carrier
Glutamine
Glutamine synthetase
diffusion
Mitochondrium
Q. Entry for all F-18 perfusion agents?
diffusion
carrier
Glutamine
Glutamine synthetase
diffusion
1 2
3 4
Mitochondrium
SUMMARY
diffusion
carrier
Glutamine
Glutamine synthetase
diffusion
Tc-99m MIBI, TF
F-18 flupiridaz and others
Ga-68 agents
Tl-201, Rb-82
Tc-99m NOET
O-15 water
Cu-62 PTSM
Tc-99m teboroxime
N-13 ammonia
C-11 ammonia
UNESCO Triple Crown in Nature & Science
Biosphere Reserve (2002)
World Natural Heritage (2007)
Global Geopark Networks (2010)
New 7 Wonders of Nature (2011)
JEJU island, no VISA entry
ISRS, May 2013
CJK, Nov 2013
AOFNMB, Oct 2015
