SPECT imaging of myocardial infarction using 99mTc-labeled C2A domain of synaptotagmin I in a porcine ischemia-reperfusion model. Nucl Med Biol 2007 Nov;34(8):917-23
Date
11/14/2007Pubmed ID
17998093DOI
10.1016/j.nucmedbio.2007.06.014Scopus ID
2-s2.0-35848929261 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
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.
Author List
Fang W, Wang F, Ji S, Zhu X, Meier HT, Hellman RS, Brindle KM, Davletov B, Zhao MMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Computer Simulation
Disease Models, Animal
Heart Ventricles
Humans
Metabolic Clearance Rate
Models, Cardiovascular
Myocardial Reperfusion Injury
Organotechnetium Compounds
Radiopharmaceuticals
Rats
Rats, Sprague-Dawley
Recombinant Fusion Proteins
Swine
Tissue Distribution
Tomography, Emission-Computed, Single-Photon