MOLECULAR IMAGING OF ATHEROSCLEROSIS USING A TC-99M-LABELED ENDOTHELIN DERIVATIVE

Endothelins have been implicated in the pathogenesis of atherosclerosi s and restenosis. The aim of this study was to characterize the potent ial of an endothelin derivative labeled with Tc-99m for imaging experi mental atherosclerosis in vivo. Methods: Atherosclerosis was induced b y balloon denudation of the infrarenal aorta in eight New Zealand whit e rabbits followed by a 6-wk period of a standard or 0.5% cholesterol diet in four animals, respectively. Another four rabbits served as con trols, without balloon denudation and cholesterol feeding. Digital sub traction angiograms and planar whole-body scintigrams were obtained af ter intravenous injection of 74 MBq of the Tc-99m-labeled endothelin d erivative. The aorta was dissected for autoradiography, sudan-ill stai ning, morphometry and immunohistology (anti-alpha-actin, RANI 11) 5 hr after injection. Results: The lesions induced in the infrarenal aorta could be detected in vivo (whole-body scintigrams) in all treated ani mals only 15 min after injection of Tc-99m-endothelin derivative. Auto radiography of the excised aorta revealed good correlation of tracer a ccumulation and sudan-ill-stained lesions. The ratio of accumulation b etween the induced lesions and untreated vessel wall was 6.8 +/- 1.4 i n the cholesterol-fed animals and 6.3 +/- 1.8 in the animals without c holesterol feeding. Accumulation of the endothelin derivative correlat ed with the number of smooth muscle cells (r = 0.924) but not with the amount of macrophages, the area or the maximum thickness of the plaqu es. Conclusion: Scintigraphic visualization of experimentally induced atherosclerosis in vivo is feasible using an endothelin derivative lab eled with (TC)-T-99m.