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.