title: Novel 18F-labeled benzofuran derivatives with improved properties for positron emission tomography (PET) imaging of β-amyloid plaques in Alzheimer's brains.
abstract: In vivo imaging of β-amyloid plaques in the brain may lead to the early diagnosis of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of treatment. In the present study, we report on the development of two potential PET probes, [(18)F]FPYBF-2 ([(18)F]10) and [(18)F]FPHBF-2 ([(18)F]21), for imaging of β-amyloid plaques in AD brain. In experiments in vitro, 10 and 21 displayed high affinity for Aβ(1-42) aggregates (K(i) = 2.41 and 3.85 nM, respectively). In biodistribution experiments using normal mice, they displayed high uptake in the brain (7.38 and 8.18% ID/g at 2 min postinjection, respectively), and the radioactivity washed out from the brain rapidly (3.15 and 3.87% ID/g at 60 min postinjection, respectively), which is highly desirable for β-amyloid imaging agents. In vivo, they clearly labeled β-amyloid plaques in Tg2576 mice. Furthermore, the specific labeling of β-amyloid plaques by 10 and 21 was observed in autoradiographs of sections of autopsied AD brain. These new fluorinated benzofuran derivatives are promising PET probes for imaging cerebral β-amyloid plaques.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan. ono@pharm.kyoto-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.forename: Shinya
authors.initials: S
authors.lastname: Kagawa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishii
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D049268:Positron-Emission Tomography; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D001572:Benzofurans