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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 ( 18 F-FOL) for the detection of atherosclerotic plaque inflammation. We studied atherosclerotic plaques in mice, rabbits, and human tissue samples using  18 F-FOL positron emission tomography/computed tomography (PET/CT). Compound 2-deoxy-2-[ 18 F]fluoro- D -glucose ( 18 F-FDG) was used as a comparison. Firstly, we found that the  in vitro  binding of  18 F-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  18 F-FOL in atherosclerotic plaques in mice and rabbits using PET/CT. We noticed that the  18 F-FOL uptake correlated with the density of macrophages in plaques and provided a target-to-background ratio as high as  18 F-FDG, but with considerably lower myocardial uptake. Thus,  18 F-FOL PET/CT targeting of FR-β-positive macrophages presents a promising new tool for the  in vivo  imaging of atherosclerotic inflammation.

Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography