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

Publication date: Available online 14 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Hiroyuki Watanabe, Taisuke Ariyoshi, Akihiko Ozaki, Masafumi Ihara, Masahiro Ono, Hideo Saji
α -Synuclein (α -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 α -syn aggregates would aid in drug development, early diagnosis, and monitoring of disease status. In order to develop imaging probes targeting α -syn aggregates, we synthesized and evaluated three novel radioiodinated benzoimidazole (BI) derivatives for selective imaging of α -syn aggregates. In binding experiments, BI-2 exhibited the highest selective binding affinity for α -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, [¹²⁵I]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 α -syn imaging probes.

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