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

Kazunari Maekawa; Atsushi B Tsuji; Atsushi Yamashita; Aya Sugyo; Chietsugu Katoh; Minghui Tang; Kensaku Nishihira; Yoshisato Shibata; Chihiro Koshimoto; Ming-Rong Zhang; Ryuichi Nishii; Keiichiro Yoshinaga; Yujiro Asada

doi:10.1016/j.atherosclerosis.2021.10.003

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

Atherosclerosis. 2021 Oct 12:337:7-17. doi: 10.1016/j.atherosclerosis.2021.10.003. Online ahead of print.

Authors

Affiliations

¹ Department of Pathology, Faculty of Medicine, University of Miyazaki, 889-1692, 5200, Kihara, Kiyotake, Miyazaki City, Miyazaki, Japan.
² Diagnostic and Therapeutic Nuclear Medicine, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 263-8555, 4-9, Anagawa, Inage, Chiba City, Chiba, Japan.
³ Department of Pathology, Faculty of Medicine, University of Miyazaki, 889-1692, 5200, Kihara, Kiyotake, Miyazaki City, Miyazaki, Japan. Electronic address: atsushi_yamashita@med.miyazaki-u.ac.jp.
⁴ Department of Biomedical Science and Engineering, Faculty of Health Sciences, Hokkaido University, 060-0812, 5, 12Jo-Nishi, Kita, Kita-Ku, Sapporo City, Hokkaido, Japan.
⁵ Department of Cardiology, Miyazaki Medical Association Hospital, 880-2102, 1173, Arita, Miyazaki City, Miyazaki, Japan.
⁶ Frontier Science Research Center, University of Miyazaki, 889-1692, 5200, Kihara, Kiyotake, Miyazaki City, Miyazaki, Japan.
⁷ Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 263-8555, 4-9, Anagawa, Inage, Chiba City, Chiba, Japan.

PMID: 34662838
DOI: 10.1016/j.atherosclerosis.2021.10.003

Abstract

Background and aims: This study aimed to investigate whether N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[¹⁸F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide (¹⁸F-FEDAC), a probe for translocator protein (TSPO), can visualize atherosclerotic lesions in rabbits and whether TSPO is localized in human coronary plaques.

Methods: ¹⁸F-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 ¹⁸F-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: ¹⁸F-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: ¹⁸F-FEDAC-PET can visualize atherosclerotic lesions, and TSPO-expression may be a marker of high-risk coronary plaques.

Keywords: Acute coronary syndrome; Atherosclerosis; Imaging; Nuclear cardiology and PET.