Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
J Med Chem. 2011 Dec 8;54(23):8085-98. doi: 10.1021/jm2009106. Epub 2011 Nov 9.
β-Amyloid plaques (Aβ plaques) in the brain are associated with cerebral amyloid angiopathy (CAA). Imaging agents that could target the Aβ plaques in the living human brain would be potentially valuable as biomarkers in patients with CAA. A new series of (18)F styrylpyridine derivatives with high molecular weights for selectively targeting Aβ plaques in the blood vessels of the brain but excluded from the brain parenchyma is reported. The styrylpyridine derivatives, 8a-c, display high binding affinities and specificity to Aβ plaques (K(i) = 2.87, 3.24, and 7.71 nM, respectively). In vitro autoradiography of [(18)F]8a shows labeling of β-amyloid plaques associated with blood vessel walls in human brain sections of subjects with CAA and also in the tissue of AD brain sections. The results suggest that [(18)F]8a may be a useful PET imaging agent for selectively detecting Aβ plaques associated with cerebral vessels in the living human brain.
脑内的β-淀粉样斑块（Aβ 斑块）与脑淀粉样血管病（CAA）有关。能够靶向活人脑内 Aβ 斑块的成像剂作为 CAA 患者的生物标志物可能具有潜在价值。报道了一系列新型（18）F 取代的苯乙烯吡啶衍生物，这些衍生物具有高分子量，可选择性地靶向脑内血管中的 Aβ 斑块，但不会进入脑实质。苯乙烯吡啶衍生物 8a-c 对 Aβ 斑块具有高的结合亲和力和特异性（K(i)分别为 2.87、3.24 和 7.71 nM）。[（18）F]8a 的体外放射自显影显示，在伴有 CAA 的受试者的人脑切片中和 AD 脑切片的组织中，与血管壁相关的β-淀粉样斑块存在放射性标记。结果表明，[（18）F]8a 可能是一种有用的 PET 成像剂，可选择性地检测活体人脑内与脑血管相关的 Aβ 斑块。
