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 - Funding Information:
We thank Erica Nyman, Marja-Riitta Kajaala, Liisa Lempiäinen, Aake Honkaniemi, Meeri Käkelä and Guru Prasad Padmasola for technical assistance, and Timo Kattelus for preparing figures. This research was conducted within the Finnish Centre of Excellence in Cardiovascular and Metabolic Diseases supported by the Academy of Finland, University of Turku, Turku University Hospital, and Åbo Akademi University. The research leading to these results was further supported by funding from the Academy of Finland (#258814 to A.R., #269213 to J.K.), the Finnish Foundation for Cardiovascular Research (to A.R., A.S., and J.K.), the Sigrid Jusélius Foundation (to A.R. & A.S.), and Jane and Aatos Erkko Foundation (to A.R.). Mass spectrometry analysis was performed at the Turku Proteomics Facility, University of Turku, and Åbo Akademi University, supported by Biocenter Finland.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
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
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 9720
ER -