title: Diphenylpropynone derivatives as probes for imaging β-amyloid plaques in Alzheimer's brains.
abstract: A new series of diphenylpropynone (DPP) derivatives for use in vivo to image β-amyloid (Aβ) plaques in the brain of patients with Alzheimer's disease (AD) were synthesized and characterized. Binding experiments in vitro revealed high affinity for Aβ (1-42) aggregates at a K(i) value ranging from 6 to 326 nM. Furthermore, specific labeling of plaques was observed in sections of brain tissue from Tg2576 transgenic mice stained using one of the compounds, 1. In biodistribution experiments with normal mice, [(125)I]1 displayed moderate uptake (1.55%ID/g at 2 min) and clearance from the brain with time (0.76 ID/g at 60 min). Taken together, DPP can serve as a new molecular scaffold for developing novel Aβ imaging agents by introducing appropriate substituted groups.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. ono@pharm.kyoto-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Rumi
authors.initials: R
authors.lastname: Watanabe
authors.forename: Mamoru
authors.initials: M
authors.lastname: Haratake
authors.forename: Morio
authors.initials: M
authors.lastname: Nakayama
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000473:pathology*; D002599:Chalcone / Q000737:chemistry / Q000493:pharmacokinetics; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015335:Molecular Probes / Q000737:chemistry* / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000737:chemistry; D058225:Plaque, Amyloid / Q000175:diagnosis*; D049268:Positron-Emission Tomography
chemical_list: D016229:Amyloid beta-Peptides; D003287:Contrast Media; D015335:Molecular Probes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D002599:Chalcone