Translocator protein imaging with 18F-FEDAC-positron emission tomography in rabbit atherosclerosis and its presence in human coronary vulnerable plaques. (November 2021)

• Record Type: Journal Article
• Authors: Maekawa, Kazunari; Tsuji, Atsushi B.; Yamashita, Atsushi; Sugyo, Aya; Katoh, Chietsugu; Tang, Minghui; Nishihira, Kensaku; Shibata, Yoshisato; Koshimoto, Chihiro; Zhang, Ming-Rong; Nishii, Ryuichi; Yoshinaga, Keiichiro; Asada, Yujiro
• Is Part Of: Atherosclerosis. Volume 337(2021)
• Page Start: 7
• Page End: 17
• Publication Date: 2021-11
• Subjects: Imaging -- Nuclear cardiology and PET -- Acute coronary syndrome -- Atherosclerosis; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2021.10.003
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: This study aimed to investigate whether N -benzyl- N -methyl-2-[7, 8-dihydro-7-(2-[ 18 F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ( 18 F-FEDAC), a probe for translocator protein (TSPO), can visualize atherosclerotic lesions in rabbits and whether TSPO is localized in human coronary plaques. Methods: 18 F-FEDAC-PET of a rabbit model of atherosclerosis induced by a 0.5% cholesterol diet and balloon injury of the left carotid artery ( n = 7) was performed eight weeks after the injury. The autoradiography intensity of 18 F-FEDAC in carotid artery tissue sections was measured, and TSPO expression was evaluated immunohistochemically. TSPO expression was examined in human coronary arteries obtained from autopsy cases ( n = 16), and in human coronary plaques ( n = 12) aspirated from patients with acute myocardial infarction (AMI). Results: 18 F-FEDAC-PET visualized the atherosclerotic lesions in rabbits as high-uptake areas, and the standard uptake value was higher in injured arteries (0.574 ± 0.24) than in uninjured arteries (0.277 ± 0.13, p < 0.05) or myocardium (0.189 ± 0.07, p < 0.05). Immunostaining showed more macrophages and more TSPO expression in atherosclerotic lesions than in uninjured arteries. TSPO was localized in macrophages, and arterial autoradiography intensity was positively correlated with macrophage concentration ( r = 0.64) and TSPO ( r = 0.67). TSPO expression in human coronary arteries was higher in AMI cases than in non-cardiac death, or in the vulnerable plaques than in early or stable lesions, respectively. TSPO was localized in macrophages in all aspirated coronary plaques with thrombi. Conclusions: 18 F-FEDAC-PET can visualize atherosclerotic lesions, and TSPO-expression may be a marker of high-risk coronary plaques. Graphical abstract: Image 1 Highlights: 18 F-FEDAC is a tracer of 18-kDa translocator protein. 18 F-FEDAC-positron emission tomography visualizes a rabbit atherosclerotic artery. Higher 18 F-FEDAC radioactivity in rabbit atherosclerotic artery than in myocardium. Translocator protein expression in macrophages in rabbit and human atherosclerosis. Translocator protein overexpression in coronary vulnerable and thrombotic plaques.