Ga-68-Labeled Benzothiazole Derivatives for Imaging A? Plaques in Cerebral Amyloid Angiopathy

Timely diagnostic imaging plays a crucial role in managing cerebral amyloid angiopathy (CAA)-the condition in which amyloid fi is deposited on blood vessels. To selectively map these amyloid plaques, we have designed amyloid-targeting ligands that can effectively complex with 68Ga3+ while maintaining good affinity for amyloid fi. In this study, we introduced novel 1,4,7triazacyclononane-based bifunctional chelators (BFCs) that incorporate a benzothiazole moiety as the Afi-binding fragment and form charged and neutral species with 68Ga3+. In vitro autoradiography using 5xFAD and WT mouse brain sections (11month-old) suggested strong and specific binding of the 68Ga complexes to amyloid fi. Biodistribution studies in CD-1 mice revealed a low brain uptake of 0.10-0.33% ID/g, thus suggesting 68Ga-labeled novel BFCs as promising candidates for detecting CAA.