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Molecular Imaging of Atherosclerosis Using a Technetium-99m-Labeled Endothelin Derivative

Research Laboratories of Schering AG, Berlin; Abteilung für Radiologische Diagnostik, Eberhard-Karls Universität Tübingen, Tübingen; Medizinische Klinik, Abteilungfür Kardiologie, Universität Ulm, Ulm; Institutfür Diagnostikforschung an der Freien Universität Berlin, Berlin, Germany

Correspondence: For correspondence or reprints contact: Luciger M. Dinkelborg, PhD, Schering AG, Forschung Molekulare Diagnostik, 13342 Berlin, Germany.

ABSTRACT

Endothelins have been implicated in the pathogenesis of atherosclerosis and restenosis. The aim of this study was to characterize the potential of an endothelin derivative labeled with ^99mTc for imaging experimental atherosclerosis in vivo. Methods: Atherosclerosis was induced by balloon denudation of the infrarenal aorta in eight New Zealand white rabbits followed by a 6-wk period of a standard or 0.5% cholesterol diet in four animals, respectively. Another four rabbits served as controls, without balloon denudation and cholesterol feeding. Digital subtraction angiograms and planar whole-body scintigrams were obtained after intravenous injection of 74 MBq of the ^99mTc-labeled endothelin derivative. The aorta was dissected for autoradiography, sudan-III staining, morphometry and immunohistology (anti-alpha-actin, RAM 11) 5 hr after injection. Results: The lesions induced in the infrarenal aorta could be detected in vivo (whole-body scintigrams) in all treated animals only 15 min after injection of ^99mTc-endothelin derivative. Autoradiography of the excised aorta revealed good correlation of tracer accumulation and sudan-III-stained lesions. The ratio of accumulation between the induced lesions and untreated vessel wall was 6.8 ± 1.4 in the cholesterol-fed animals and 6.3 ± 1.8 in the animals without cholesterol feeding. Accumulation of the endothelin derivative correlated 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 plaques. Conclusion: Scintigraphic visualization of experimentally induced atherosclerosis in vivo is feasible using an endothelin derivative labeled with ^99mTc.

Key Words: balloon angioplasty • restenosis • neointimal formation • radiopharmaceuticals • techetium-99m-ZK 167054

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