title: 6-Methoxy-indanone derivatives as potential probes for β-amyloid plaques in Alzheimer's disease.
abstract: A series of 6-methoxy indanone derivatives was synthesized and evaluated as potential probes for β-amyloid plaque imaging in Alzheimer's disease (AD). Two derivatives (5d and 5k) displayed significant binding abilities in fluorescent staining experiments using the brain sections of AD patients. Two derivatives showed high binding affinities to β-amyloid aggregates (5j, Ki= 5.82 ± 0.19 nM) and brain homogenates of AD patients (5j, Ki= 18.96 ± 0.28 nM) in in vitro binding assay. With a log P value of 3.45, [125I]5k exhibited an excellent initial brain uptake (5.29%ID g-1, 2 min after i.v.) and a fast clearance from the brain in biodistribution experiments in normal mice. In autoradiography, [125I]5k exhibited an obvious binding ability to β-amyloid plaques and a relatively low nonspecific binding in the brain sections of AD patients (in vitro) and APP/PS1 transgenic mice (in vitro and ex vivo). Results suggest that 5k is a potential probe for detecting β-amyloid plaques in vivo.
authors: CAS Key Laboratory of Brain Function and Disease, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230027, PR China.
authors: Dou-Dou
authors: DD
authors: Nan
authors: Engineering Research Centre of Bio-process of Ministry of Education, Hefei University of Technology, Hefei, Anhui, 230009, PR China.
authors: Chang-Sheng
authors: CS
authors: Gan
authors: CAS Key Laboratory of Brain Function and Disease, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230027, PR China.
authors: Chen-Wei
authors: CW
authors: Wang
authors: Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, PR China.
authors: Jin-Ping
authors: JP
authors: Qiao
authors: CAS Key Laboratory of Brain Function and Disease, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230027, PR China.
authors: Xin-Meng
authors: XM
authors: Wang
authors: CAS Key Laboratory of Brain Function and Disease, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230027, PR China. Electronic address: jnzhou@ustc.edu.cn.
authors: Jiang-Ning
authors: JN
authors: Zhou
mesh_terms: D000544:Alzheimer Disease / Q000150:complications*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D004355:Drug Stability; D007189:Indans / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D058225:Plaque, Amyloid / Q000150:complications* / Q000000981:diagnostic imaging* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D007189:Indans; D015335:Molecular Probes
keywords: Alzheimer's disease; Amyloid probes; Indanone; Molecular imaging; β-amyloid plaques