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

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.