Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63108.
Proc Natl Acad Sci U S A. 2020 Dec 8;117(49):30928-30933. doi: 10.1073/pnas.2014058117. Epub 2020 Nov 24.
Herein, we report a Cu positron emission tomography (PET) imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of wild-type mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable blood-brain barrier penetration, while the use of optimized-length spacers between the Cu-chelating group and the Aβ-interacting fragments further improves the in vivo Aβ-binding specificity and brain uptake of the corresponding Cu PET imaging agent.
在此，我们报告了一种铜正电子发射断层扫描（PET）成像剂，该成像剂在体内具有可观的脑摄取，并对β-淀粉样蛋白（Aβ）聚集体表现出高特异性亲和力，从而成功地对 5xFAD 小鼠大脑中的淀粉样斑块进行了 PET 成像，而对野生型小鼠则没有。所采用的方法使用了一种双功能螯合剂，其中包含两个与 Aβ相互作用的片段，这极大地提高了 Aβ的结合亲和力和亲脂性，有利于穿透血脑屏障，而在铜螯合基团和 Aβ相互作用片段之间使用优化长度的间隔物则进一步提高了相应的 Cu PET 成像剂的体内 Aβ结合特异性和脑摄取。
