Synthesis and biological evaluation of novel radioiodinated imidazopyridine derivatives for amyloid-β imaging in Alzheimer's disease.
Autor: | Chen CJ; Fujifilm RI Pharma Co. LTD, Chiba, Japan; Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan; The United Graduate School of Veterinary Science, Gifu University, Gifu, Japan., Bando K; Fujifilm RI Pharma Co. LTD, Chiba, Japan., Ashino H; Fujifilm RI Pharma Co. LTD, Chiba, Japan., Taguchi K; Fujifilm RI Pharma Co. LTD, Chiba, Japan., Shiraishi H; Fujifilm RI Pharma Co. LTD, Chiba, Japan., Fujimoto O; Fujifilm RI Pharma Co. LTD, Chiba, Japan., Kitamura C; Fujifilm RI Pharma Co. LTD, Chiba, Japan., Matsushima S; Fujifilm RI Pharma Co. LTD, Chiba, Japan., Fujinaga M; Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan., Zhang MR; Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan., Kasahara H; Fujifilm RI Pharma Co. LTD, Chiba, Japan., Minamizawa T; Fujifilm RI Pharma Co. LTD, Chiba, Japan., Jiang C; School of Pharmacy, Fudan University, Shanghai, China., Ono M; Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan., Higuchi M; Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan., Suhara T; Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan., Yamada K; The United Graduate School of Veterinary Science, Gifu University, Gifu, Japan. Electronic address: kyamada@obihiro.ac.jp., Ji B; Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan. Electronic address: kihin@nirs.go.jp. |
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Jazyk: | angličtina |
Zdroj: | Bioorganic & medicinal chemistry [Bioorg Med Chem] 2014 Aug 01; Vol. 22 (15), pp. 4189-97. Date of Electronic Publication: 2014 Jun 02. |
DOI: | 10.1016/j.bmc.2014.05.043 |
Abstrakt: | Non-invasive detection for amyloid-β peptide (Aβ) deposition has important significance for the early diagnosis and medical intervention for Alzheimer's disease (AD). In this study, we developed a series of imidazopyridine derivatives as potential imaging agents for single-photon emission computed tomography (SPECT). Two of them, compounds DRK092 and DRM106, showed higher affinity for synthetic human Aβ 1-40 fibrils than did the well-known amyloid-imaging agent IMPY. A metabolite analysis revealed brain-permeable radioactive metabolites of (125)I-labeled DRK092 and IMPY; no radioactive metabolites from (125)I-labeled DRM106 ([(125)I]DRM106) were detected. In addition, in vitro autoradiography clearly demonstrated specific binding of [(125)I]DRM106 in the hippocampal region of AD enriched with Aβ plaques. Thus, our results strongly suggested that compound DRM106 can be used as an imaging agent for SPECT to detect Aβ deposition in AD brain. (Copyright © 2014 Elsevier Ltd. All rights reserved.) |
Databáze: | MEDLINE |
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