Novel chalcones as probes for in vivo imaging of ƒÀ-amyloid plaques in Alzheimer's brains.
ABSTRACT
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.