Development of amyloid imaging PET probes for an early diagnosis of Alzheimer's disease.

Progressive accumulation of senile plaques (SPs) is one of the major neuropathological features of Alzheimer's Disease (AD) that precedes cognitive decline. Noninvasive detection of SPs could, therefore, be a potential diagnostic test for early or presymptomatic detection of AD patients. For this purpose, many attempts have been made to visualize AD-specific pathological changes in the living brain. Currently, a most practical method for the in vivo measurement of SP depositions is using positron emission tomography (PET) and contrast agent that specifically label SPs. We have developed a novel compound 2-[2-(2-dimethylaminothiazol-5-yl) ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole (BF-227) as a candidate for an amyloid imaging probe for PET. BF-227 displayed high affinity to synthetic amyloid beta fibrils and clearly stained both SPs and diffuse plaques in AD brain sections. Intravenous administration of [11C]BF-227 into normal mice indicated that this labeled tracer readily penetrated the blood brain barrier (BBB) and was washed out quickly from brain tissue. Currently, we have investigated the clinical trial of [11C]BF-227 in healthy subjects and AD patients.