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

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 alumin...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0ba0ded919c04de1bea8c1128f7cd5be
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spelling	oai:doaj.org-article:0ba0ded919c04de1bea8c1128f7cd5be2021-12-02T15:09:09ZAluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography10.1038/s41598-018-27618-42045-2322https://doaj.org/article/0ba0ded919c04de1bea8c1128f7cd5be2018-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-27618-4https://doaj.org/toc/2045-2322Abstract 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.Johanna M. U. SilvolaXiang-Guo LiJenni VirtaPäivi MarjamäkiHeidi LiljenbäckJarkko P. HytönenMiikka TarkiaVirva SaunavaaraSaija HurmeSenthil PalaniHarri HakovirtaSeppo Ylä-HerttualaPekka SaukkoQingshou ChenPhilip S. LowJuhani KnuutiAntti SarasteAnne RoivainenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography
description	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.
format	article
author	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
author_facet	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
author_sort	Johanna M. U. Silvola
title	Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography
title_short	Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography
title_full	Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography
title_fullStr	Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography
title_full_unstemmed	Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography
title_sort	aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/0ba0ded919c04de1bea8c1128f7cd5be
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Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography

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