In vivo dynamic imaging of myocardial cell death using ^99mTc-labeled C2A domain of synaptotagmin I in a rat model of ischemia and reperfusion

Objectives: This study was designed to investigate the capability of a small-animal SPECT imager, FastSPECT II, for dynamic rat heart imaging and to characterize the in vivo kinetic properties of ^99mTc-C2A-glutathione-s-transferase (GST), a molecular probe targeting apoptosis and necrosis, in detecting cell death in ischemic-reperfused rat hearts. Methods: C2A-GST was radiolabeled with ^99mTc via 2-iminothiolane thiolation. Myocardial ischemia-reperfusion was induced by 30-min ligation of the left coronary artery followed by 120-min reperfusion in seven rats. FastSPECT II cardiac images of ^99mTc-C2A-GST in list-mode acquisition were recorded for 2 h using FastSPECT II. Results: Tomographic images showed a focal radioactive accumulation (hot spot) in the lateral and anterior walls of the left ventricle. The hot spot was initially visualized 10 min after injection and persisted on the 2-h images. Quantitative analysis demonstrated that the hot-spot radioactivity increased significantly within 30 min postinjection and experienced no washout up to the end of the 2-h study. The ratio of the hot spot/viable myocardium was 4.52±0.24, and infarct-to-lung ratio was 8.22±0.63 at 2 h postinjection. The uptake of ^99mTc-C2A-GST in the infarcted myocardium was confirmed by triphenyl tetrazolium chloride staining and autoradiography analysis. Conclusions: FastSPECT II allows quantitative dynamic imaging and functional determination of radiotracer kinetics in rat hearts. An in vivo kinetic profile of ^99mTc-C2A-GST in the ischemic-reperfused rat heart model was characterized successfully. The pattern of accelerated ^99mTc-C2A-GST uptake in the ischemic area at risk after reperfusion may be useful in detecting and quantifying ongoing myocardial cell loss induced by ischemia-reperfusion.