title: In vivo SPECT imaging of amyloid-β deposition with radioiodinated imidazo[1,2-a]pyridine derivative DRM106 in a mouse model of Alzheimer's disease.
abstract: Noninvasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention for Alzheimer's disease (AD). In the present study, we investigated the availability of radiolabeled DRM106 ((123/125)I-DRM106 [6-iodo-2-[4-(1H-3-pyrazolyl)phenyl]imidazo[1,2-a]pyridine]), a compound with sufficient affinity for the synthesis of human Aβ fibrils and satisfactory metabolic stability, as a SPECT ligand in living brains.
  
  
  METHODS
  The sensitivity of (125)I-DRM106 for detecting Aβ deposition was compared with that of (125)I-IMPY (2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), a well-known amyloid SPECT ligand, by ex vivo autoradiographic analyses in 18-mo-old amyloid precursor protein transgenic mice. To verify the sensitivity and quantitation of radiolabeled DRM106 for in vivo imaging, we compared the detectability of Aβ plaques with (123)I-DRM106 and a well-known amyloid PET agent, (11)C-labeled Pittsburgh compound B ((11)C-PiB), in 29-mo-old transgenic mice and age-matched nontransgenic littermates. Additionally, we compared the binding characteristics of (125)I-DRM106 with those of (11)C-PiB and (11)C-PBB3, which selectively bind to Aβ plaques and preferentially to tau aggregates, respectively, in postmortem AD brain sections.
  
  
  RESULTS
  Ex vivo autoradiographic analysis showed that measurement with (125)I-DRM106 has a higher sensitivity for detecting Aβ accumulation than with (125)I-IMPY in transgenic mice. SPECT imaging with (123)I-DRM106 also successfully detected Aβ deposition in living aged transgenic mice and showed strong correlation (R = 0.95, P < 0.01) in quantitative analysis for Aβ plaque detection by PET imaging with (11)C-PiB, implying that sensitivity and quantitation of SPECT imaging with (123)I-DRM106 are almost as good as (11)C-PiB PET for the detectability of Aβ deposition. Further, the addition of nonradiolabeled DRM106 fully blocked the binding of (125)I-DRM106 and (11)C-PiB, but not (11)C-PBB3, to AD brain sections, and (125)I-DRM106 showed a lower binding ratio of the diffuse plaque-rich lateral temporal cortex to the dense-cored/neuritic plaque-rich hippocampal CA1 area, compared with (11)C-PiB.
  
  
  CONCLUSIONS
  All of these data demonstrated the high potential of (123)I-DRM106 for amyloid imaging in preclinical and clinical application, and it might more preferentially detect dense-cored/neuritic amyloid deposition, which is expected to be closely associated with neuropathologic changes of 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; and.
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: Satoshi
authors.initials: S
authors.lastname: Matsushima
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD, Chiba, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Research Department, Fujifilm RI Pharma Co. LTD, Chiba, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Nakahara
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: Maiko
authors.initials: M
authors.lastname: Ono
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Tokunaga
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; and.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan kihin@nirs.go.jp.
authors.forename: Bin
authors.initials: B
authors.lastname: Ji
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C000595794:6-iodo-2-(4-(1H-3-pyrazolyl)phenyl)imidazo(1,2-a)pyridine; D016229:Amyloid beta-Peptides; D007093:Imidazoles; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D011725:Pyridines; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C023666:pyridine
keywords: Alzheimer’s disease (AD); DRM106; amyloid imaging; amyloid precursor protein (APP) transgenic mouse; single photon emission computed tomography (SPECT)