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

<div> <p>The design, synthesis, and properties of a new gadolinium-based copper-responsive MRI contrast agents are presented in detail here. The sensor (GdL<sub>1</sub>) has high selectivity for copper ions and exhibits a 47% increase in r<sub>1</sub> relaxivity upon binding to 1 equivalent of Cu<sup>2+</sup> in aqueous buffer. Interestingly, in the presence of physiological levels of human serum albumin (HSA), the r<sub>1</sub> relaxivity is amplified even further up to 270%. Additional spectroscopic and XAS studies show that Cu<sup>2+</sup> is coordinated by two carboxylic acid groups and the single amine group on an appended side-chain of GdL<sub>1</sub> and forms a ternary complex with HSA (GdL<sub>1</sub>-Cu<sup>2+</sup>-HSA). T<sub>1</sub>-weighted <i>in vivo</i> imaging demonstrates that GdL<sub>1</sub> 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.</p> </div>