University of Oulu

Hellberg, S.; Silvola, J.M.; Liljenbäck, H.; Kiugel, M.; Eskola, O.; Hakovirta, H.; Hörkkö, S.; Morisson-Iveson, V.; Hirani, E.; Saukko, P.; Ylä-Herttuala, S.; Knuuti, J.; Saraste, A.; Roivainen, A. Amyloid-Targeting PET Tracer [18F]Flutemetamol Accumulates in Atherosclerotic Plaques. Molecules 2019, 24, 1072.

Amyloid-targeting PET tracer [¹⁸F]Flutemetamol accumulates in atherosclerotic plaques

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Author: Hellberg, Sanna1; Silvola, Johanna M.U.1; Liljenbäck, Heidi1,2;
Organizations: 1Turku PET Centre, University of Turku, FI-20520 Turku, Finland
2Turku Center for Disease Modeling, University of Turku, FI-20520 Turku, Finland
3Department of Vascular Surgery, Turku University Hospital, FI-20520 Turku, Finland
4Medical Research Center and Nordlab Oulu, University Hospital and Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, FI-90014 Oulu, Finland
5GE Healthcare Ltd., Chalfont St Giles HP8 4SP, UK
6Department of Pathology and Forensic Medicine, University of Turku, FI-20520 Turku, Finland
7A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70210 Kuopio, Finland
8Turku PET Centre, Turku University Hospital, FI-20520 Turku, Finland
9Heart Center, Turku University Hospital, FI-20520 Turku, Finland
10Department of Clinical Medicine, University of Turku, FI-20520 Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.9 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019071923145
Language: English
Published: Multidisciplinary Digital Publishing Institute, 2019
Publish Date: 2019-07-19
Description:

Abstract

Atherosclerosis is characterized by the accumulation of oxidized lipids in the artery wall, which triggers an inflammatory response. Oxidized low-density lipoprotein (ox-LDL) presents amyloid-like structural properties, and different amyloid species have recently been recognized in atherosclerotic plaques. Therefore, we studied the uptake of the amyloid imaging agent [¹⁸F]Flutemetamol in atherosclerotic plaques. The binding of [¹⁸F]Flutemetamol to human carotid artery plaque was studied in vitro. In vivo uptake of the tracer was studied in hypercholesterolemic IGF-II/LDLR⁻/⁻ApoB¹⁰⁰/¹⁰⁰ mice and C57BL/6N controls. Tracer biodistribution was studied in vivo with PET/CT, and ex vivo by gamma counter and digital ex vivo autoradiography. The presence of amyloid, ox-LDL, and macrophages in the plaques was examined by immunohistochemistry. [¹⁸F]Flutemetamol showed specific accumulation in human carotid plaque, especially in areas positive for amyloid beta. The aortas of IGF-II/LDLR⁻/⁻ApoB¹⁰⁰/¹⁰⁰ mice showed large thioflavin-S-positive atherosclerotic plaques containing ox-LDL and macrophages. Autoradiography revealed 1.7-fold higher uptake in the plaques than in a lesion-free vessel wall, but no difference in aortic tissue uptake between mouse strains were observed in the in vivo PET/CT. In conclusion, [¹⁸F]Flutemetamol binds to amyloid-positive areas in human atherosclerotic plaques. Further studies are warranted to clarify the uptake mechanisms, and the potential of the tracer for in vivo imaging of atherosclerosis in patients.

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Series: Molecules
ISSN: 1420-3049
ISSN-E: 1420-3049
ISSN-L: 1420-3049
Volume: 24
Issue: 6
Article number: 1072
DOI: 10.3390/molecules24061072
OADOI: https://oadoi.org/10.3390/molecules24061072
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
3121 General medicine, internal medicine and other clinical medicine
Subjects:
Funding: This study 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 was further supported by funding from the Finnish Cultural Foundation/Varsinais-Suomi Regional Fund, Turku University Foundation, Sigrid Jusélius Foundation, Jane and Aatos Erkko Foundation, Finnish Foundation for Cardiovascular Research, and Ida Montin Foundation.
Copyright information: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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