68Ga-Labeled Benzothiazole Derivatives for Imaging Aβ Plaques in Cerebral Amyloid Angiopathy.

Abstract

Timely diagnostic imaging plays a crucial role in managing cerebral amyloid angiopathy (CAA)—the condition in which amyloid β 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 β. In this study, we introduced novel 1,4,7-triazacyclononane-based bifunctional chelators (BFCs) that incorporate a benzothiazole moiety as the Aβ-binding fragment and form charged and neutral species with 68Ga3+. In vitro autoradiography using 5xFAD and WT mouse brain sections (11-month-old) suggested strong and specific binding of the 68Ga complexes to amyloid β. 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.