Radioiodinated benzimidazole derivatives as single photon emission computed tomography probes for imaging of β-amyloid plaques in Alzheimer's disease

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• 作者：Mengchao Cui^a ; ^b ; Masahiro Ono^a ; ^{ono@pharm.kyoto-u.ac.jp} ; Hiroyuki Kimura^a ; Hidekazu Kawashima^a ; Bo Li Liu^b ; Hideo Saji^a ; ^{hsaji@pharm.kyoto-u.ac.jp}
• 关键词：Alzheimer's disease ; β ; -Amyloid ; Single photon emission computed tomography (SPECT) ; Imaging agent
• 刊名：Nuclear Medicine and Biology
• 出版年：2011
• 出版时间：April 2011
• 年：2011
• 卷：38
• 期：3
• 页码：313-320
• 全文大小：723 K

文摘

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 [¹²⁵I]12, labeled Aβ plaques selectively with low nonspecific binding. Biodistribution experiments with normal mice injected intravenously with [¹²⁵I]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, [¹²⁵I]12 labeled amyloid plaques in vivo in an AD transgenic model. The preliminary results strongly suggest that [¹²⁵I]12 bears characteristics suitable for detecting amyloid plaques in vivo. When labeled with ¹²³I, it may be a useful SPECT imaging agent for Aβ plaques in the brain of living AD patients.