title: Biological evaluation of the radioiodinated imidazo[1,2-a]pyridine derivative DRK092 for amyloid-β imaging in mouse model of Alzheimer's disease.
abstract: Non-invasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention in Alzheimer's disease (AD). In this study, we investigated the availability of a radioiodinated imidazo[1,2-a]pyridine derivative, termed (125)I-DRK092, as single photon emission computed tomography (SPECT) ligand for in vivo detection of Aβ deposition. DRK092 showed high binding affinity for either synthetic human Aβ fibrils or brain homogenates from amyloid precursor protein transgenic (Tg) mouse (PS1-ki/JU-Tg2576) and AD patient with a dissociation constant (Kd) of one-digit nM, and excellent brain permeability (peak value of uptake: approximately 0.9% of injection dose/g rat brain). Ex vivo autoradiographic analysis showed that measurement with (125)I-DRK092 has higher sensibility for detecting Aβ accumulation than with (125)I-IMPY, a well-known amyloid SPECT ligand, in Tg mice. In vitro autoradiography with (125)I-DRK092 also confirmed higher accumulation of radioactivity in the cortical area, enriched with Aβ plaques, of Tg mouse and AD patient brains, as compared with the corresponding areas in non-Tg mouse and healthy control brains. All the data presented above lead us to draw the conclusion that radioiodinated DRK092 is a potential SPECT ligand for amyloid imaging in AD.
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD., Chiba, Japan; Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; Clinical Veterinary Science, The United Graduate School of Veterinary Science, Gifu University, Gifu, Japan.
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD., Chiba, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Bando
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD., Chiba, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ashino
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD., Chiba, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD., Chiba, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shiraishi
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD., Chiba, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Shima
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD., Chiba, Japan.
authors.forename: Osuke
authors.initials: O
authors.lastname: Fujimoto
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD., Chiba, Japan.
authors.forename: Chiemi
authors.initials: C
authors.lastname: Kitamura
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD., Chiba, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Morimoto
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD., Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kasahara
authors.affiliation: Research Department, 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, Chiba, Japan.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: Clinical Veterinary Science, 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, Chiba, Japan. Electronic address: kihin@nirs.go.jp.
authors.forename: Bin
authors.initials: B
authors.lastname: Ji
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D051379:Mice; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D011720:Pyrazoles; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D016229:Amyloid beta-Peptides; C000598412:DRK092; D007093:Imidazoles; D007457:Iodine Radioisotopes; D011720:Pyrazoles; D011725:Pyridines; C000971:2,3-dihydro-1H-imidazo(1,2-b)pyrazole; C023666:pyridine
keywords: Alzheimer's disease (AD); Amyloid precursor protein (APP) transgenic mouse; Amyloid-β peptide (Aβ); DRK092; IMPY; Single photon emission computed tomography (SPECT)