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  • Title: Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography.
    Author: Silvola JMU, Li XG, Virta J, Marjamäki P, Liljenbäck H, Hytönen JP, Tarkia M, Saunavaara V, Hurme S, Palani S, Hakovirta H, Ylä-Herttuala S, Saukko P, Chen Q, Low PS, Knuuti J, Saraste A, Roivainen A.
    Journal: Sci Rep; 2018 Jun 26; 8(1):9720. PubMed ID: 29946129.
    Abstract:
    Inflammation plays an important role in the development of atherosclerosis and its complications. Because the folate receptor β (FR-β) is selectively expressed on macrophages, an FR targeted imaging agent could be useful for assessment of atherosclerotic inflammation. We investigated aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid conjugated folate (18F-FOL) for the detection of atherosclerotic plaque inflammation. We studied atherosclerotic plaques in mice, rabbits, and human tissue samples using 18F-FOL positron emission tomography/computed tomography (PET/CT). Compound 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) was used as a comparison. Firstly, we found that the in vitro binding of 18F-FOL co-localized with FR-β-positive macrophages in carotid endarterectomy samples from patients with recent ischemic symptoms. We then demonstrated specific accumulation of intravenously administered 18F-FOL in atherosclerotic plaques in mice and rabbits using PET/CT. We noticed that the 18F-FOL uptake correlated with the density of macrophages in plaques and provided a target-to-background ratio as high as 18F-FDG, but with considerably lower myocardial uptake. Thus, 18F-FOL PET/CT targeting of FR-β-positive macrophages presents a promising new tool for the in vivo imaging of atherosclerotic inflammation.
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