SPECT imaging of myocardial infarction using ^99mTc-labeled C2A domain of synaptotagmin I in a porcine ischemia-reperfusion model

Introduction: 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.