Refereed journal article or data article (A1)
Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography
List of Authors: Johanna M. U. Silvola, Xiang-Guo Li, Jenni Virta, Päivi Marjamäki, Heidi Liljenbäck, Jarkko P. Hytönen, Miikka Tarkia, Virva Saunavaara, Saija Hurme, Senthil Palani, Harri Hakovirta, Seppo Ylä-Herttuala, Pekka Saukko, Qingshou Chen, Philip S. Low, Juhani Knuuti, Antti Saraste, Anne Roivainen
Publisher: NATURE PUBLISHING GROUP
Publication year: 2018
Journal: Scientific Reports
Journal name in source: SCIENTIFIC REPORTS
Journal acronym: SCI REP-UK
Article number: ARTN 9720
Volume number: 8
Number of pages: 15
ISSN: 2045-2322
eISSN: 2045-2322
DOI: http://dx.doi.org/10.1038/s41598-018-27618-4
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/32165321
Inflammation plays an important role in the development of atherosclerosis and its complications. Because the folate receptor beta (FR-beta) 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 (F-18-FOL) for the detection of atherosclerotic plaque inflammation. We studied atherosclerotic plaques in mice, rabbits, and human tissue samples using F-18-FOL positron emission tomography/computed tomography (PET/CT). Compound 2-deoxy-2-[F-18]fluoro-D-glucose (F-1(8)-FDG) was used as a comparison. Firstly, we found that the in vitro binding of F-18-FOL co-localized with FR-beta-positive macrophages in carotid endarterectomy samples from patients with recent ischemic symptoms. We then demonstrated specific accumulation of intravenously administered F-18-FOL in atherosclerotic plaques in mice and rabbits using PET/CT. We noticed that the F-18-FOL uptake correlated with the density of macrophages in plaques and provided a target-to-background ratio as high as F-18-FDG, but with considerably lower myocardial uptake. Thus, F-18-FOL PET/CT targeting of FR-beta-positive macrophages presents a promising new tool for the in vivo imaging of atherosclerotic inflammation.
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