title: Novel imaging agents for β-amyloid plaque based on the N-benzoylindole core.
abstract: We report the synthesis and evaluation of a series of N-benzoylindole derivatives as novel potential imaging agents for β-amyloid plaques. In vitro binding studies using Aβ(1-40) aggregates versus [(125)I]TZDM showed that all these derivatives demonstrated high binding affinities (K(i) values ranged from 8.4 to 121.6 nM). Moreover, two radioiodinated compounds [(125)I]7 and [(125)I]14 were prepared. Autoradiography for [(125)I]14 displayed intense and specific labeling of Aβ plaques in the brain sections of AD model mice (C57, APP/PS1) with low background. In vivo biodistribution in normal mice exhibited sufficient initial brain uptake for imaging (2.19% and 2.00%ID/g at 2 min postinjection for [(125)I]7 and [(125)I]14, respectively). Although additional modifications are necessary to improve brain uptake and clearance from the brain, the N-benzoylindole may be served as a backbone structure to develop novel β-amyloid imaging probes.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Duan
authors.forename: Jun-Yuan
authors.initials: JY
authors.lastname: Deng
authors.forename: Bing
authors.initials: B
authors.lastname: Jin
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Jia
authors.forename: Bo-Li
authors.initials: BL
authors.lastname: Liu
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015335:Molecular Probes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D015394:Molecular Structure; D058225:Plaque, Amyloid / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D007211:Indoles; D015335:Molecular Probes