机构：[a]Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China[b]Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China首都医科大学宣武医院[c]Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan 430074, PR China[d]Beijing ZHIBO Bio-Medical Technology Co. Ltd., Beijing 102502, PR China
A new series of fluoro-pegylated benzyloxybenzenes were designed, synthesized and evaluated as PET probes for early detection of A beta plaques. Molecular docking revealed that all of the flexible benzyloxybenzenes inserted themselves into the hydrophobic Va118_Phe20 cleft on the flat spine of the A beta fiber, in a manner similar to that of IMPY molecule. The most potent probe, [F-18]9a, exhibited a combination of high binding affinity to A beta aggregates (K-i= 21.0 +/- 4.9 nM), high initial brain uptake (9.14% ID/g at 2 min), fast clearance from normal brain tissue (1.79% ID/g at 60 min), and satisfactory in vivo biostability in the brain (95% of intact form at 2 min). [F-18]9a clearly labeled A beta plaques in in vitro autoradiography of postmortem AD patients and Tg mice brain sections. Ex vivo autoradiography further demonstrated that [F-18]9a did penetrate the intact BBB and specifically bind to A beta plaques in vivo. Overall, [F-18]9a may be a potential PET probe for imaging A beta plaques in AD brains. (C) 2015 Elsevier Masson SAS. All rights reserved.
基金：
the National Natural Science Foundation of China (No. 21201019)
the National Science and Technology Major Projects for Major New Drugs Innovation and Development (No. 2014ZX09507007-002).
第一作者机构：[a]Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China
通讯作者：
通讯机构：[a]Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China[b]Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China
推荐引用方式(GB/T 7714)：
Yanping Yang,Hualong Fu,Mengchao Cui,et al.Preliminary evaluation of fluoro-pegylated benzyloxybenzenes for quantification of beta-amyloid plaques by positron emission tomography[J].EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY.2015,104:86-96.doi:10.1016/j.ejmech.2015.09.028.
APA：
Yanping Yang,Hualong Fu,Mengchao Cui,Cheng Peng,Zhigang Liang...&Boli Liu.(2015).Preliminary evaluation of fluoro-pegylated benzyloxybenzenes for quantification of beta-amyloid plaques by positron emission tomography.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,104,
MLA：
Yanping Yang,et al."Preliminary evaluation of fluoro-pegylated benzyloxybenzenes for quantification of beta-amyloid plaques by positron emission tomography".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 104.(2015):86-96
医学