Binding and safety profile of novel benzoxazole derivative for in vivo imaging of amyloid deposits in Alzheimer's disease

Abstract

Background: In vivo detection of amyloid deposits in the brain is potentially useful for early diagnosis of Alzheimer's disease (AD) and tracking the efficacy of anti‐amyloid therapy.Methods: To develop an amyloid‐binding agent for positron emission tomography, we screened over 2600 compounds.Results: We found benzoxazole derivatives as candidate compounds for in vivo amyloid imaging probes. One of these agents, 2‐(2‐[2‐dimethylaminothiazol‐5‐yl]ethenyl)‐6‐(2‐[fluoro]ethoxy)benzoxazole (BF‐227), displays high binding affinity to Aβ fibrils. BF‐227 binding increased linearly with increasing Aβ fibril formation. In temporal and hippocampal AD brain sections, BF‐227 selectively bound to amyloid plaques. In contrast, no staining was evident in the cerebellum. Compared with the previously reported compound BF‐168, 18F‐labeled BF‐227 displayed selective in vivo labeling of amyloid fibrils and rapid washout from white matter areas in an Aβ‐injected rat model. An acute and subacute toxicity study of BF‐227 indicated sufficient safety for clinical use as a positron emission tomography probe.Conclusions: These findings suggest that BF‐227 is feasible as an in vivo imaging probe of amyloid deposits in AD patients.