title: Novel quinoxaline derivatives for in vivo imaging of β-amyloid plaques in the brain.
abstract: In a search for new probes to detect β-amyloid plaques in the brain of patients with Alzheimer's disease (AD), we have synthesized and evaluated a series of quinoxaline derivatives containing a '6+6-6' ring system. These quinoxaline derivatives showed excellent affinity for Aβ(1-42) aggregates with K(i) values ranging from 2.6 to 10.7nM. Autoradiography with sections of brain tissue from an animal model of AD mice (APP/PS1) and AD patients revealed that [(125)I]5 labeled β-amyloid plaques specifically. In biodistribution experiments using normal mice, [(125)I]5 displayed high uptake (6.03% ID/g at 2min) into and a moderately fast washout from the brain. Although additional refinements are needed to decrease the lipophilicity and improve the washout rate, the quinoxaline scaffold may be useful as a backbone structure to develop novel β-amyloid imaging agents.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.forename: Boli
authors.initials: B
authors.lastname: Liu
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D011485:Protein Binding; D011810:Quinoxalines / Q000737:chemistry* / Q000493:pharmacokinetics; D011859:Radiography; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D011810:Quinoxalines; D019275:Radiopharmaceuticals; C075222:amyloid beta-protein (1-42)