Cargando…

Amyloid-Targeting PET Tracer [(18)F]Flutemetamol Accumulates in Atherosclerotic Plaques

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 p...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471324/
https://www.ncbi.nlm.nih.gov/pubmed/30893771
http://dx.doi.org/10.3390/molecules24061072
Descripción
Sumario: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 [(18)F]Flutemetamol in atherosclerotic plaques. The binding of [(18)F]Flutemetamol to human carotid artery plaque was studied in vitro. In vivo uptake of the tracer was studied in hypercholesterolemic IGF-II/LDLR(−/−)ApoB(100/100) 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. [(18)F]Flutemetamol showed specific accumulation in human carotid plaque, especially in areas positive for amyloid beta. The aortas of IGF-II/LDLR(−/−)ApoB(100/100) 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, [(18)F]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.