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A Responsive MRI Contrast Agent for Detection of Excess copper(II) in the Liver in Vivo

preprint
submitted on 19.11.2018 and posted on 20.11.2018 by Namini Paranawithana, Andre F. Martins, Veronica Clavijo-Jordan, Piyu Zhao, Sara Chirayil, Gabriele Meloni, Dean Sherry

The design, synthesis, and properties of a new gadolinium-based copper-responsive MRI contrast agents are presented in detail here. The sensor (GdL1) has high selectivity for copper ions and exhibits a 47% increase in r1 relaxivity upon binding to 1 equivalent of Cu2+ in aqueous buffer. Interestingly, in the presence of physiological levels of human serum albumin (HSA), the r1 relaxivity is amplified even further up to 270%. Additional spectroscopic and XAS studies show that Cu2+ is coordinated by two carboxylic acid groups and the single amine group on an appended side-chain of GdL1 and forms a ternary complex with HSA (GdL1-Cu2+-HSA). T1-weighted in vivo imaging demonstrates that GdL1 can detect basal, endogenous labile copper(II) ions in living mice. This offers a unique opportunity to explore the role of copper ions in the development and progression of neurological diseases such as Wilson disease.

Funding

NIH DK-095416

NIH EB-015908

Robert A. Welch AT-584

Robert A. Welch At-1935

History

Email Address of Submitting Author

dean.sherry@utsouthwestern.edu

Institution

University of Texas at Dallas and University of Texas Southwestern Medical Center

Country

USA

ORCID For Submitting Author

0000-0001-7150-8301

Declaration of Conflict of Interest

No conflicts

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in Journal of the American Chemical Society

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