title: Radioiodinated benzimidazole derivatives as single photon emission computed tomography probes for imaging of β-amyloid plaques in Alzheimer's disease.
abstract: Five iodinated 2-phenyl-1H-benzo[d]imidazole derivatives were synthesized and evaluated as potential probes for β-amyloid (Aβ) plaques. One of the compounds, 4-(6-iodo-1H-benzo[d]imidazol-2-yl)-N,N-dimethylaniline (12), showed excellent affinity for Aβ(1-42) aggregates (K(i) = 9.8 nM). Autoradiography with sections of postmortem Alzheimer's disease (AD) brain revealed that a radioiodinated probe [(125)I]12, labeled Aβ plaques selectively with low nonspecific binding. Biodistribution experiments with normal mice injected intravenously with [(125)I]12 showed high uptake [4.14 percent injected dose per gram (% ID/g) at 2 min] into and rapid clearance (0.15% ID/g at 60 min) from the brain, which may bring about a good signal-to-noise ratio and therefore achieve highly sensitive detection of Aβ plaques. In addition, [(125)I]12 labeled amyloid plaques in vivo in an AD transgenic model. The preliminary results strongly suggest that [(125)I]12 bears characteristics suitable for detecting amyloid plaques in vivo. When labeled with (123)I, it may be a useful SPECT imaging agent for Aβ plaques in the brain of living AD patients.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kawashima
authors.forename: Bo Li
authors.initials: BL
authors.lastname: Liu
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry* / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D055815:Young Adult
chemical_list: D016229:Amyloid beta-Peptides; D001562:Benzimidazoles; D007457:Iodine Radioisotopes; C031000:benzimidazole