Synthesis and evaluation of ethyleneoxylated and allyloxylated chalcone derivatives for imaging of amyloid β plaques by SPECT

We report radioiodinated chalcone derivatives as new SPECT imaging probes for amyloid beta (A beta) plaques. The monoethyleneoxy derivative 2 and allyloxy derivative 8 showed a high affinity for A beta(1-42) aggregates with K-i values of 24 and 4.5 nM, respectively. Fluorescent imaging demonstrated that 2 and 8 clearly stained thioflavin-S positive A beta plaques in the brain sections of Tg2576 transgenic mice. In vitro autoradiography revealed that [I-125]2 displayed no clear accumulation toward A beta plaques in the brain sections of Tg2576 mice, whereas the accumulation pattern of [I-125]8 matched with the presence of A beta plaques both in the brain sections of Tg2576 mice and an AD patient. In biodistribution studies using normal mice, [I-125]2 showed preferable in vivo pharmacokinetics (4.82%ID/g at 2 min and 0.45%ID/g at 60 min), while [I-125]8 showed only a modest brain uptake (1.62%ID/g at 2 min) with slow clearance (0.56%ID/g at 60 min). [I-125]8 showed prospective binding properties for A beta plaques, although further structural modifications are needed to improve the blood brain barrier permeability and washout from brain. (C) 2014 Elsevier Ltd. All rights reserved.