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High-performance Photoacoustic Probe for Biopsy-free Assessment of Copper Status in Murine Models of Wilson’s Disease and Liver Metastasis

preprint
submitted on 10.04.2021, 06:33 and posted on 12.04.2021, 13:01 by Melissa Lucero, Yuqi Tang, Chloe Zhang, ShengZhang Su, Joseph Forzano, Valeria Garcia, Xin Huang, David Moreno, Jefferson Chan

The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep-tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be highly optimized for in vivo performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, the first PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wildtype mice, as well as elevated Cu in a Wilson’s disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted a blind study where we were able to successfully identify a Wilson’s disease animal from a group of healthy control mice with greater than 99.7% confidence.

Funding

National Science Foundation (1752879)

History

Email Address of Submitting Author

jeffchan@illinois.edu

Institution

University of Illinois at Urbana-Champaign

Country

United States

ORCID For Submitting Author

0000-0003-4139-4379

Declaration of Conflict of Interest

No conflict of interest

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