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.