Novel chalcones as probes for in vivo imaging of ƒÀ-amyloid plaques in Alzheimer's brains.
A novel series of chalcone derivatives for in vivo imaging ƒÀ-amyloid plaques in the brain of Alzheimer's disease (AD) were synthesized and characterized. When in vitro binding studies using AƒÀ aggregates were carried out with chalcone derivatives, the binding affinities for AƒÀ aggregate varied from 3 to 105 nM. The radioiodinated chalcones were successfully prepared through an iododestannylation reaction from the corresponding tributyltin derivatives using hydrogen peroxide as the oxidant in high yields and with high radiochemical purities. Biodistribution studies in normal mice after iv injection of the radioiodinated chalcones displayed high brain uptake (2.0-4.7% ID/g at 2 min) and rapid clearance from the brain (0.2-0.6% ID/g at 30 min), which is highly desirable for amyloid imaging agents. The results in this study suggest that the novel radioiodinated chalcones may be useful amyloid imaging agents for detecting ƒÀ-amyloid plaques in the brain of AD.