SPECT imaging of myocardial infarction using 99mTc-labeled C2A domain of synaptotagmin I in a porcine ischemia-reperfusion model.
BACKGROUND
The C2A domain of synaptotagmin I recognizes necrotic and apoptotic cells by binding to exposed anionic phospholipids. The goal is to explore the potential imaging utility of 99mTc-labeled C2A in the detection of acute cardiac cell death in a porcine model that resembles human cardiovascular physiology.


METHODS
Ischemia (20-25 min) was induced in pigs (M/F, 20-25 kg) using balloon angioplasty. 99mTc-C2A-GST (n=7) or 99mTc-BSA (n=2) was injected intravenously 1-2 h after reperfusion. Noninfarct animals were injected with 99mTc-C2A-GST (n=4). SPECT images were acquired at 3 and 6 h postinjection. Cardiac tissues were analyzed to confirm the presence of cell death.


RESULTS
Focal uptake was detected in five out of seven subjects at 3 h and in all infarct subjects at 6 h postinjection but not in infarct animals injected with 99mTc-BSA or in noninfarct animals with 99mTc-C2A-GST. Gamma counting of infarct versus normal myocardium yielded a 10.2+/-5.7-fold elevation in absolute radioactivity, with histologically confirmed infarction.


CONCLUSIONS
We present data on imaging myocardial cell death in the acute phase of infarction in pigs. C2A holds promise and warrants further development as an infarct-avid molecular probe.
Fang
Wei
W
Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China.
Wang
Feng
F
Ji
Shundong
S
Zhu
Xiaoguang
X
Meier
Heidi T
HT
Hellman
Robert S
RS
Brindle
Kevin M
KM
Davletov
Bazbek
B
Zhao
Ming
M
D000818:Animals; D017209:Apoptosis; D003198:Computer Simulation; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008657:Metabolic Clearance Rate; D008955:Models, Cardiovascular; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics*; D013552:Swine; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; C526993:technetium 99m C2A-glutathione transferase