title: Synthesis and Monkey-PET Study of (R)- and (S)-18F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive in Vivo Kinetics.
abstract: This study describes an effective strategy to improve pharmacokinetics of Aβ imaging agents, offering a novel class of (R)- and (S)-18F-labeled 2-arylbenzoheterocyclic derivatives which bear an additional chiral hydroxyl group on the side chain. These ligands displayed binding abilities toward Aβ aggregates with Kivalues ranging from 3.2 to 195.6 nM. Chirality-related discrepancy was observed in biodistribution, and (S)-2-phenylbenzoxazole enantiomers exhibited vastly improved brain clearance with washout ratios higher than 20. Notably, (S)-[18F]28 possessed high binding potency (Ki= 7.6 nM) and exceptional brain kinetics (9.46% ID/g at 2 min, brain2min/brain60min= 27.8) that is superior to well-established [18F]AV45. The excellent pharmacokinetics and low nonspecific binding of (S)-[18F]28 were testified by dynamic PET/CT scans in monkey brains. In addition, (S)-[18F]28 clearly labeled Aβ plaques both in vitro and ex vivo. These results might qualify (S)-[18F]28 to detect Aβ plaques with high signal-to-noise ratio.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, P. R. 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, P. R. China.
authors.forename: Xuedan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Chinese PLA General Hospital , Beijing 100853, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, P. R. China.
authors.forename: Hualong
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Nuclear Medicine, Chinese PLA General Hospital , Beijing 100853, P. R. China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Chinese PLA General Hospital , Beijing 100853, P. R. China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities , Wuhan 430074, P. R. China.
authors.forename: Jiapei
authors.initials: J
authors.lastname: Dai
authors.affiliation: Beijing ZHIBO Bio-Medical Technology Co. Ltd. , Beijing 102502, P. R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing ZHIBO Bio-Medical Technology Co. Ltd. , Beijing 102502, P. R. China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Lin
authors.affiliation: Beijing ZHIBO Bio-Medical Technology Co. Ltd. , Beijing 102502, P. R. China.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , Beijing 100875, P. R. China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D000818:Animals; D005462:Fluorine Radioisotopes; D000882:Haplorhini; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*
chemical_list: D005462:Fluorine Radioisotopes
keywords: Alzheimer’s disease; molecular imaging; positron emission tomography; β-amyloid plaque