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

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Jun 20

PMID 35721913

Authors

Truc T Huynh

Yujue Wang

Karna Terpstra

Hong-Jun Cho

Liviu M Mirica

Buck E Rogers

Affiliations

Soon will be listed here.

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 Ga 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 Ga. In vitro autoradiography using 5xFAD and WT mouse brain sections (11-month-old) suggested strong and specific binding of the 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 Ga-labeled novel BFCs as promising candidates for detecting CAA.

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