title: Synthesis and biological evaluation of 18F-labled 2-phenylindole derivatives as PET imaging probes for β-amyloid plaques.
abstract: A novel series of fluorinated 2-phenylindole derivatives were synthesized and evaluated as β-amyloid imaging probes for PET. The in vitro inhibition assay demonstrated that their binding affinities for Aβ(1-42) aggregates ranged from 28.4 to 1097.8 nM. One ligand was labeled with (18)F ([(18)F]1a) for its high affinity (K(i)=28.4 nM), which was also confirmed by in vitro autoradiography experiments on brain sections of transgenic mouse (C57BL6, APPswe/PSEN1, 11 months old, male). In vivo biodistribution experiments in normal mice showed that this radiotracer displayed high initial uptake (5.82±0.51% ID/g at 2 min) into and moderate washout (2.77±0.31% ID/g at 60 min) from the brain. [(18)F]1a could be developed as a promising new PET imaging probe for Aβ plaques although necessary modifications are still needed.
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.forename: Lihai
authors.initials: L
authors.lastname: Yu
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.forename: Zijing
authors.initials: Z
authors.lastname: Li
authors.forename: Xuedan
authors.initials: X
authors.lastname: Wang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Jia
authors.forename: Yanping
authors.initials: Y
authors.lastname: Yang
authors.forename: Pingrong
authors.initials: P
authors.lastname: Yu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Jia
authors.forename: Boli
authors.initials: B
authors.lastname: Liu
mesh_terms: D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000032:analysis* / Q000378:metabolism; D058225:Plaque, Amyloid / Q000175:diagnosis*; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D005462:Fluorine Radioisotopes; D007211:Indoles; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C542223:2-phenylindole