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淀粉样蛋白靶向 PET 示踪剂 [F]氟替美莫在动脉粥样硬化斑块中积累。

Amyloid-Targeting PET Tracer [F]Flutemetamol Accumulates in Atherosclerotic Plaques.

机构信息

Turku PET Centre, University of Turku, FI-20520 Turku, Finland.

Turku Center for Disease Modeling, University of Turku, FI-20520 Turku, Finland.

出版信息

Molecules. 2019 Mar 19;24(6):1072. doi: 10.3390/molecules24061072.

DOI:10.3390/molecules24061072
PMID:30893771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6471324/
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 [F]Flutemetamol in atherosclerotic plaques. The binding of [F]Flutemetamol to human carotid artery plaque was studied in vitro. In vivo uptake of the tracer was studied in hypercholesterolemic IGF-II/LDLRApoB 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. [F]Flutemetamol showed specific accumulation in human carotid plaque, especially in areas positive for amyloid beta. The aortas of IGF-II/LDLRApoB 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, [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.

摘要

动脉粥样硬化的特征是氧化脂质在动脉壁中的积累，这引发了炎症反应。氧化低密度脂蛋白（ox-LDL）呈现出类似淀粉样的结构特性，最近在动脉粥样硬化斑块中已经识别出不同的淀粉样物质。因此，我们研究了淀粉样成像剂[F]Flutemetamol在动脉粥样硬化斑块中的摄取。我们在体外研究了[F]Flutemetamol与人颈动脉斑块的结合。在高胆固醇血症 IGF-II/LDLRApoB 小鼠和 C57BL/6N 对照中研究了示踪剂的体内摄取。使用 PET/CT 研究了示踪剂的体内生物分布，并用伽马计数器和数字离体放射自显影术进行了离体研究。通过免疫组织化学检查斑块中淀粉样蛋白、ox-LDL 和巨噬细胞的存在。[F]Flutemetamol在人颈动脉斑块中表现出特异性积累，尤其是在淀粉样β阳性区域。IGF-II/LDLRApoB 小鼠的主动脉显示出大的硫黄素-S 阳性动脉粥样硬化斑块，含有 ox-LDL 和巨噬细胞。放射自显影显示斑块的摄取比无病变的血管壁高 1.7 倍，但在体内 PET/CT 中未观察到两种小鼠品系的主动脉组织摄取差异。总之，[F]Flutemetamol与人类动脉粥样硬化斑块中的淀粉样阳性区域结合。需要进一步的研究来阐明摄取机制，以及该示踪剂在患者体内动脉粥样硬化成像中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138a/6471324/40ce90430153/molecules-24-01072-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138a/6471324/40ce90430153/molecules-24-01072-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138a/6471324/40ce90430153/molecules-24-01072-g005.jpg

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