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

Five iodinated 2-phenyl- l H-benzo[d]imidazole derivatives were synthesized and evaluated as potential probes for beta-amyloid (A beta) plaques. One of the compounds, 4-(6-iodo- l H-benzo[d]imidazol-2-yl)-N,N-dimethylaniline (12), showed excellent affinity for A beta(1-42) aggregates (K-i=9.8 nM). Autoradiography with sections of postmortem Alzheimer's disease (AD) brain revealed that a radioiodinated probe [I-125]12, labeled A beta plaques selectively with low nonspecific binding. Biodistribution experiments with normal mice injected intravenously with [I-125]12 showed high uptake [4.14 percent injected close per gram (% ID/g) at 2 min] into and rapid clearance (0.15% lD/g at 60 min) from the brain, which may bring about a good signal-to-noise ratio and therefore achieve highly sensitive detection of A beta plaques. In addition, [I-125]12 labeled amyloid plaques in vivo in an AD transgenic model. The preliminary results strongly suggest that [I-125]12 bears characteristics suitable for detecting amyloid plaques in vivo. When labeled with I-123, it may be a useful SPECT imaging agent for A beta plaques in the brain of living AD patients. (C) 2011 Elsevier Inc. All rights reserved.