OBJECTIVEApoptosis contributes to the instability of the atherosclerotic (AS) lesions. The vulnerable plaque was identified in vivo by detecting the apoptosis with radiolabeled annexin V in an atherosclerotic rabbit model.

METHODSEight male New Zealand white rabbits on 2% cholesterol diet for 2 weeks had abdominal aortic balloon injury and fed a 2% cholesterol diet for another 15 weeks (AS group), 3 rabbits fed a normal rabbit chow for 17 weeks without balloon injury served as controls. Annexin V labeled with (99)Tc(m) was then intravenously administered and planar whole-body images were captured using a gamma camera in the left lateral position. The entire length of the abdominal aorta was explanted for ex vivo imaging with gamma camera. The aorta then was divided into several segments according to the severity of AS. The segments were separated weighted and counted in an gamma counter for the absorptive dose of annexin per gram of tissue. Histology examinations were made on specimens.

RESULTSAt 2 hours post annexin V injection, clear delineation of radiolabel within the abdominal aorta could be evidenced in vivo gamma imaging. After explanation of the aorta, ex vivo imaging showed a robust uptake of radiotracer in the infradiaphragmatic aorta corresponding to the in vivo images and conforming to the macroscopic distribution of atherosclerotic lesions. The uptake of radiolabel was absent in areas without grossly visible atherosclerotic lesions. The in vivo and ex vivo images identified plaque areas were identical and corresponded histological results on the explanted specimen. The aortic specimen was divided into 18 segments on lesions. The magority of the lesions (14/18) manifested as type IV or type V lesions of AHA classification (vulnerable lesions), except segments 1 - 4, which manifested as type I or type II lesions. The thickness of fibrous cap (TFC) and the ratio of cap and lipid nuclear (RCN) were significantly reversely correlated to the unit radioactivity counts, and the correlation between RCN and the unit radioactivity counts was more significant than that between TFC and the unit radioactivity counts (r = -0.904, P < 0.01, and r = -0.8, P < 0.01). Apoptosis detection (TUNEL): annexin V intake in plaques was positively correlated to apoptotic index(r = 0.651, P = 0.012).

CONCLUSIONNoninvasive Annexin V imaging could be used to detect vulnerable atherosclerotic plaques in vivo.