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

作者：Truc T. Huynh, Yujue Wang, Karna Terpstra, Hong‐Jun Cho, Liviu M. Mirica, Buck E. Rogers · 发表于：ACS Omega · 年份：2022 · DOI：10.1021/acsomega.2c02369 · 被引用次数：9 · 研究领域：Alzheimer's disease research and treatments、Amyloidosis: Diagnosis, Treatment, Outcomes、S100 Proteins and Annexins

High Resolution Image Download MS PowerPoint Slide 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 68 Ga 3+ 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 68 Ga 3+ . In vitro autoradiography using 5xFAD and WT mouse brain sections (11-month-old) suggested strong and specific binding of the 68 Ga complexes to amyloid β. Biodistribution studies in CD-1 mice revealed a low brain uptake of 0.10–0.33% ID/g, thus suggesting 68 Ga-labeled novel BFCs as promising candidates for detecting CAA.