title: Preliminary evaluation of fluoro-pegylated benzyloxybenzenes for quantification of β-amyloid plaques by positron emission tomography.
abstract: A new series of fluoro-pegylated benzyloxybenzenes were designed, synthesized and evaluated as PET probes for early detection of Aβ plaques. Molecular docking revealed that all of the flexible benzyloxybenzenes inserted themselves into the hydrophobic Val18_Phe20 cleft on the flat spine of the Aβ fiber, in a manner similar to that of IMPY molecule. The most potent probe, [(18)F]9a, exhibited a combination of high binding affinity to Aβ aggregates (Ki = 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). [(18)F]9a clearly labeled Aβ plaques in in vitro autoradiography of postmortem AD patients and Tg mice brain sections. Ex vivo autoradiography further demonstrated that [(18)F]9a did penetrate the intact BBB and specifically bind to Aβ plaques in vivo. Overall, [(18)F]9a may be a potential PET probe for imaging Aβ plaques in AD brains.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Hualong
authors.initials: H
authors.lastname: Fu
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China. Electronic address: cmc@bnu.edu.cn.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China. Electronic address: zg_liang1972@sina.com.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan 430074, PR China.
authors.forename: Jiapei
authors.initials: J
authors.lastname: Dai
authors.affiliation: Beijing ZHIBO Bio-Medical Technology Co. Ltd., Beijing 102502, PR China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing ZHIBO Bio-Medical Technology Co. Ltd., Beijing 102502, PR China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Lin
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Boli
authors.initials: B
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D001921:Brain; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D062105:Molecular Docking Simulation; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D058225:Plaque, Amyloid / Q000737:chemistry* / Q000378:metabolism; D049268:Positron-Emission Tomography
chemical_list: D016229:Amyloid beta-Peptides; D001555:Benzene Derivatives; D015335:Molecular Probes
keywords: Alzheimer's disease; Benzyloxybenzenes; F-18 tracer; PET imaging; β-Amyloid plaques