A Responsive Magnetic Resonance Imaging Contrast Agent for Detection of Excess Copper(II) in the Liver In Vivo

Namini N. Paranawithana, Andre F. Martins, Veronica Clavijo Jordan, Piyu Zhao, Sara Chirayil, Gabriele Meloni, Dean Sherry

Research output: Contribution to journalArticle

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Abstract

The design, synthesis, and properties of a new gadolinium-based copper-responsive magnetic resonance imaging (MRI) contrast agent is presented. The sensor (GdL1) has high selectivity for copper ions and exhibits a 43% increase in r1 relaxivity (20 MHz) upon binding to 1 equiv of Cu2+ in aqueous buffer. Interestingly, in the presence of physiological levels of human serum albumin (HSA), the r1 relaxivity is amplified further up to 270%. Additional spectroscopic and X-ray absorption spectroscopy (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's disease.

Original languageEnglish (US)
Pages (from-to)11009-11018
Number of pages10
JournalJournal of the American Chemical Society
Volume141
Issue number28
DOIs
Publication statusPublished - Jul 17 2019

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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