Development of alkoxy styrylchromone derivatives for imaging of cerebral amyloid-β plaques with SPECT

We report here the development of radioiodinated styrylchromone derivatives with alkoxy groups as single photon emission computed tomography (SPECT) imaging probes for cerebral amyloid-beta (A beta) plaques. Among the derivatives, the methoxy derivative 14 and the dimethoxy derivative 15 displayed relatively high affinity for the A beta(1-42) aggregates with K-i values of 22 and 46 nM, respectively. Fluorescent imaging demonstrated that 14 and 15 clearly labeled thioflavin-S positive A beta plaques in the brain sections of Tg2576 transgenic mice. In the in vivo studies, [I-125]14 and [I-125]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 [I-125]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 A beta plaques in the brain. In particular, further structural modifications are required to improve the compounds binding affinity for A beta. (C) 2015 Elsevier Ltd. All rights reserved.