Open Access68Ga-Labeled Benzothiazole Derivatives for Imaging Aβ Plaques in Cerebral Amyloid Angiopathy
Author(s) -
Truc T. Huynh,
Yujue Wang,
Karna Terpstra,
HongJun Cho,
Liviu M. Mirica,
Buck E. Rogers
Publication year - 2022
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.2c02369
Subject(s) - benzothiazole , cerebral amyloid angiopathy , biodistribution , amyloid (mycology) , pittsburgh compound b , moiety , chemistry , in vitro , pathology , biochemistry , biophysics , medicine , alzheimer's disease , biology , dementia , stereochemistry , disease
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.