Synthesis and biological evaluation of novel radioiodinated benzimidazole derivatives for imaging α-synuclein aggregates

alpha-Synuclein (alpha-syn) aggregates are commonly found in the brains of patients with Parkinson's disease (PD), dementia with Lewy bodies (DLB), and some other diseases. Therefore, in vivo imaging of alpha-syn aggregates would aid in drug development, early diagnosis, and monitoring of disease status. In order to develop imaging probes targeting alpha-syn aggregates, we synthesized and evaluated three novel radioiodinated benzimidazole (BI) derivatives for selective imaging of alpha-syn aggregates. In binding experiments, BI-2 exhibited the highest selective binding affinity for alpha-syn aggregates among the BI derivatives. In addition, BI-2 clearly stained Lewy bodies in PD brain sections, but did not label senile plaques deposited in AD brain sections. However, in the biodistribution study using normal mice, [I-125]BI-2 did not demonstrate high brain uptake (0.56% ID/g at 2-min post-injection). Further structural modifications of the BI derivatives are needed, but the BI scaffold may be an attractive candidate for developing alpha-syn imaging probes. (C) 2017 Elsevier Ltd. All rights reserved.