title: ¹⁸F-labeled 2-phenylquinoxaline derivatives as potential positron emission tomography probes for in vivo imaging of β-amyloid plaques.
abstract: In continuation of our study on the 2-phenylquinoxaline scaffold as potential β-amyloid imaging probes, two [(18)F]fluoro-pegylated 2-phenylquinoxaline derivatives, 2-(4-(2-[(18)F]fluoroethoxy)phenyl)-N-methylquinoxalin-6-amine ([(18)F]4a) and 2-(4-(2-(2-(2-[(18)F]fluoroethoxy)ethoxy)ethoxy)phenyl)-N-methylquinoxalin-6-amine ([(18)F]4b) were prepared. Both of them displayed high binding affinity to Aβ(1-42) aggregates (K(i) = 10.0 ± 1.4 nM for 4a, K(i) = 5.3 ± 3.2 nM for 4b). The specific and high binding of [(18)F]4a and [(18)F]4b to Aβ plaques was confirmed by in vitro autoradiography on brain sections of AD human and transgenic mice. In biodistribution in normal mice, [(18)F]4a displayed high initial brain uptake (8.17% ID/g at 2 min) and rapid washout from the brain. These preliminary results suggest [(18)F]4a may be a potential PET imaging agent for Aβ plaques in the living human brain.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Pingrong
authors.initials: P
authors.lastname: Yu
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.forename: Xuedan
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.forename: Zijing
authors.initials: Z
authors.lastname: Li
authors.forename: Yanping
authors.initials: Y
authors.lastname: Yang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Jia
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhang
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
authors.forename: Hongmei
authors.initials: H
authors.lastname: Jia
authors.forename: Boli
authors.initials: B
authors.lastname: Liu
mesh_terms: D016229:Amyloid beta-Peptides / Q000648:ultrastructure*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000648:ultrastructure*; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011859:Radiography; D013194:Staining and Labeling / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D003287:Contrast Media; D005462:Fluorine Radioisotopes; D010446:Peptide Fragments; D011810:Quinoxalines; C075222:amyloid beta-protein (1-42)