Amyloid-targeting PET tracer [¹⁸F]Flutemetamol accumulates in atherosclerotic plaques
Hellberg, Sanna; Silvola, Johanna M.U.; Liljenbäck, Heidi; Kiugel, Max; Eskola, Olli; Hakovirta, Harri; Hörkkö, Sohvi; Morisson-Iveson, Veronique; Hirani, Ella; Saukko, Pekka; Ylä-Herttuala, Seppo; Knuuti, Juhani; Saraste, Antti; Roivainen, Anne (2019-03-19)
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
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https://urn.fi/URN:NBN:fi-fe2019071923145
Tiivistelmä
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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