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

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 <i>r</i>₁ 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 <i>r</i>₁ 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). <i>T</i>₁-weighted <i>in vivo</i> 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.