99mTc-annexin V imaging for in vivo detection of atherosclerotic lesions in porcine coronary arteries.

Abstract

UNLABELLED: We used a model of porcine coronary atherosclerosis characterized by smooth muscle cell apoptosis to test the hypothesis that apoptosis of cells in the vascular wall of coronary arteries can be detected on SPECT images using a technetium-labeled radiotracer that targets apoptosis. METHODS: Eleven juvenile male swine received a high-fat diet combined with injury to 22 coronary vessels. After 51 +/- 9 d (mean +/- SD), the animals underwent coronary angiography, were injected with 403.3 +/- 48.1 MBq of 99mTc-annexin V, underwent SPECT, and were sacrificed. The coronary arteries underwent autoradiography and well counting, and immunostaining was performed for alpha-actin, caspase, and macrophages. RESULTS: Atherosclerotic lesions were predominantly of American Heart Association class II. Thirteen of the 22 injured vessels showed focal uptake of 99mTc-annexin V in vivo (scan positive), and 9 injured vessels and all control vessels showed no focal uptake (scan negative). The count ratios of the injured vessels to the control vessels were 2.38 +/- 0.61 for scan-positive vessels and 1.27 +/- 0.23 for scan-negative vessels (P < 0.001). The percentages of injected dose for the scan-positive and scan-negative vessels were 1.73 +/- 0.83 x 10(-3) and 0.68 +/- 0.20 x 10(-3), respectively (P < 0.001). Immunohistopathologic examination found that the cells undergoing apoptosis were smooth muscle cells. The apoptotic index (caspase-positive cells to total cells) was 63% +/- 7% for scan-positive vessels and 16% +/- 10% for scan-negative vessels (P < 0.001). Both the count ratio of injured vessels to control vessels and the percentage injected dose correlated significantly with death rate by regression analysis. CONCLUSION: Annexin is a noninvasive method to identify plaque apoptosis in the coronary vessels.