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

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.