TY - JOUR
T1 - Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography
AU - Silvola, Johanna M.U.
AU - Li, Xiang Guo
AU - Virta, Jenni
AU - Marjamäki, Päivi
AU - Liljenbäck, Heidi
AU - Hytönen, Jarkko P.
AU - Tarkia, Miikka
AU - Saunavaara, Virva
AU - Hurme, Saija
AU - Palani, Senthil
AU - Hakovirta, Harri
AU - Ylä-Herttuala, Seppo
AU - Saukko, Pekka
AU - Chen, Qingshou
AU - Low, Philip S.
AU - Knuuti, Juhani
AU - Saraste, Antti
AU - Roivainen, Anne
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/6/26
Y1 - 2018/6/26
N2 - 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.
AB - 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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U2 - 10.1038/s41598-018-27618-4
DO - 10.1038/s41598-018-27618-4
M3 - Article
C2 - 29946129
AN - SCOPUS:85049221403
SN - 2045-2322
VL - 8
SP - 9720
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 9720
ER -