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Metal-Chelating Benzothiazole Multifunctional Compounds for the Modulation and 64Cu PET Imaging of Aβ Aggregation

submitted on 04.06.2020, 04:15 and posted on 05.06.2020, 05:05 by Yiran Huang, Hong-Jun Cho, Nilantha Bandara, Liang Sun, Diana Tran, Buck E. Rogers, Liviu M. Mirica
While Alzheimer’s Disease (AD) is the most common neurodegenerative disease, there is still a dearth of efficient therapeutic and diagnostic agents for this disorder. Reported herein are a series of new multifunctional compounds (MFCs) with appreciable affinity for amyloid aggregates that can be potentially used for both the modulation of Ab aggregation and its toxicity, as well as positron emission tomography (PET) imaging of Ab aggregates. Firstly, among the six compounds tested HYR-16 is shown to be capable to reroute the toxic Cu-mediated Ab oligomerization into the formation of less toxic amyloid fibrils. In addition, HYR-16 can also alleviate the formation of reactive oxygen species (ROS) caused by Cu2+ ions through Fenton-like reactions. Secondly, these MFCs can be easily converted to PET imaging agents by pre-chelation with the 64Cu radioisotope, and the Cu complexes of HYR-4 and HYR-17 exhibit good fluorescent staining and radiolabeling of amyloid plaques both in vitro and ex vivo. Importantly, the 64Cu-labeled HYR-17 is shown to have a significant brain uptake of up to 0.99 ± 0.04 %ID/g. Overall, by evaluating the various properties of these MFCs valuable structure-activity relationships were obtained that should aid the design of improved therapeutic and diagnostic agents for AD.


NIH R01GM114588


Email Address of Submitting Author


University of Illinois at Urbana-Champaign



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest

Version Notes

Version 1.0