Development of alkoxy styrylchromone derivatives for imaging of cerebral
amyloid-b plaques with SPECT
ABSTRACT
We report here the development of radioiodinated styrylchromone derivatives
with alkoxy groups as single photon emission computed tomography (SPECT)
imaging probes for cerebral amyloid-b (Ab) plaques. Among the derivatives,
the methoxy derivative 14 and the dimethoxy derivative 15 displayed relatively
high affinity for the Ab(1–42) aggregates with Ki values of 22 and 46 nM,
respectively. Fluorescent imaging demonstrated that 14 and 15 clearly labeled
thioflavin-S positive Ab plaques in the brain sections of Tg2576 transgenic
mice. In the in vivo studies, [125I]14 and [125I]15 showed high initial
brain uptake expressed as the percentage of the injected dose per gram
(2.25% and 2.49% ID/g at 2 min, respectively) with favorable clearance
(0.12% and 0.20% ID/g at 180 min, respectively) from the brain tissue of
normal mice. Furthermore, in vitro autoradiography confirmed that [125I]15
binds thioflavin-S positive regions in Tg2576 mouse brain sections. The
derivative 15 may be a potential scaffold for the development of in vivo
imaging probes targeting Ab plaques in the brain. In particular, further
structural modifications are required to improve the compounds binding
affinity for Ab.