title: Synthesis and biological evaluation of novel radioiodinated imidazopyridine derivatives for amyloid-β imaging in Alzheimer's disease.
abstract: 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.
authors.affiliation: 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.
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Fujifilm RI Pharma Co. LTD, Chiba, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Bando
authors.affiliation: Fujifilm RI Pharma Co. LTD, Chiba, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ashino
authors.affiliation: Fujifilm RI Pharma Co. LTD, Chiba, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Fujifilm RI Pharma Co. LTD, Chiba, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shiraishi
authors.affiliation: Fujifilm RI Pharma Co. LTD, Chiba, Japan.
authors.forename: Osuke
authors.initials: O
authors.lastname: Fujimoto
authors.affiliation: Fujifilm RI Pharma Co. LTD, Chiba, Japan.
authors.forename: Chiemi
authors.initials: C
authors.lastname: Kitamura
authors.affiliation: Fujifilm RI Pharma Co. LTD, Chiba, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsushima
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.affiliation: Fujifilm RI Pharma Co. LTD, Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kasahara
authors.affiliation: Fujifilm RI Pharma Co. LTD, Chiba, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Minamizawa
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Ono
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.affiliation: The United Graduate School of Veterinary Science, Gifu University, Gifu, Japan. Electronic address: kyamada@obihiro.ac.jp.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan. Electronic address: kihin@nirs.go.jp.
authors.forename: Bin
authors.initials: B
authors.lastname: Ji
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D007457:Iodine Radioisotopes / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D016229:Amyloid beta-Peptides; C000598412:DRK092; D007093:Imidazoles; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D011725:Pyridines; D019275:Radiopharmaceuticals; C078592:amyloid beta-protein (1-40)
keywords: Alzheimer’s disease (AD); Amyloid-β peptide (Aβ); Autoradiography; Positron emission tomography (PET); Single-photon emission computed tomography (SPECT)