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Novel TSPO ligand 18F-FEMPA: biodistribution and uptake into atherosclerotic plaques in mice




List of AuthorsSanna E. Hellberg, Johanna M.U. Silvola, Max Kiugel, Heidi Liljenbäck, Nina Savisto, Andrea Thiele, V. Jukka O. Laine, Juhani Knuuti, Anne Roivainen, Antti Saraste

Publication year2015

JournalEHJ Cardiovascular Imaging / European Heart Journal - Cardiovascular Imaging

Journal acronymEur Heart J Cardiovasc Imaging

Volume number16

Issue numberSuppl 1

Start pagei59

End pagei69


Abstract

Purpose: Inflammation in atherosclerotic plaques is associated with higher risk of cardiac events. Radioligands targeting the 18 kDa translocator protein (TSPO) expressed on activated macrophages have been proposed for molecular imaging of inflammation in atherosclerosis. We evaluated the feasibility of 18F-FEMPA, a novel TSPO ligand radiolabeled for positron emission tomography (PET) imaging, for the detection of vascular inflammation in a mouse model of atherosclerosis.

Methods: Uptake of 18F-FEMPA was analyzed in hypercholesterolemic mice deficient of the low-density lipoprotein receptor expressing only apolipoprotein B100 (LDLR-/-ApoB100/100, n = 9) and in healthy C57BL/6N mice (n = 7). Twenty minutes after intravenous injection of 18F-FEMPA, tissue samples were obtained for analysis of biodistribution, and aortas were cut into sections for autoradiography, histology and immunohistochemistry of macrophages (Mac-3) and TSPO.

Results: Aortas of atherosclerotic LDLR-/-ApoB100/100 mice showed large atherosclerotic plaques with extensive macrophage infiltration. The clearance of 18F-FEMPA from blood circulation was rapid and the aorta-to-blood ratio was 4.8 at 20 minutes post-injection in the LDLR-/-ApoB100/100 mice. The accumulation of 18F-FEMPA in the aorta was higher in the LDLR-/-ApoB100/100 than in healthy mice (P = 0.03), whereas radioactivity in the blood was comparable. Autoradiography showed 18F-FEMPA uptake in atherosclerotic plaques, but it also extended to the non-atherosclerotic vessel wall. Tracer uptake was significantly higher in plaques with high than low macrophage content (count densities 330 ± 110 versus 210 ± 47 photo-stimulated luminescence per square millimeter, P = 0.0024). Furthermore, high tracer uptake in plaques co-localized with macrophage-rich areas, and immunohistochemistry showed co-localization of TSPO and macrophages.

Conclusions: PET tracer 18F-FEMPA shows rapid clearance from blood and high degree of accumulation into the aorta of atherosclerotic mice. Its accumulation in macrophage-rich atherosclerotic plaques suggests potential for imaging of vascular inflammation.



Last updated on 2021-24-06 at 11:44