title: Synthesis and biological evaluation of novel oxindole derivatives for imaging neurofibrillary tangles in Alzheimer's disease.
abstract: This letter describes the synthesis and biological evaluation of a novel series of radioiodinated oxindole (OI) derivatives for detecting neurofibrillary tangles (NFTs) in the brains of patients with Alzheimer's disease (AD). In binding experiments in vitro, 2-oxindole (2-OI) and 3-oxindole (3-OI) derivatives showed affinity for tau aggregates. The 3-OI derivative 14 showed the highest affinity of these derivatives. In biodistribution experiments using normal mice, the OI derivatives displayed good uptake (2.4-2.5%ID/g at 2 min) and clearance from the brain with time (0.6-1.4%ID/g at 30 min). In fluorescence staining experiments using AD brain sections, 14 clearly stained NFTs. 3-OI may serve as a new molecular scaffold for developing novel NFT imaging agents.
authors: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Hiroyuki
authors: H
authors: Watanabe
authors: Masahiro
authors: M
authors: Ono
authors: Hiroyuki
authors: H
authors: Kimura
authors: Kenji
authors: K
authors: Matsumura
authors: Masashi
authors: M
authors: Yoshimura
authors: Yoko
authors: Y
authors: Okamoto
authors: Masafumi
authors: M
authors: Ihara
authors: Ryosuke
authors: R
authors: Takahashi
authors: Hideo
authors: H
authors: Saji
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D000078183:Oxindoles; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D014018:Tissue Distribution; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: D007211:Indoles; D007457:Iodine Radioisotopes; D000078183:Oxindoles; D016875:tau Proteins; C022960:2-oxindole