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

• Published in: Journal of the American Chemical Society Vol. 141; no. 28; pp. 11009 - 11018
• Main Authors: Paranawithana, Namini N, Martins, Andre F, Clavijo Jordan, Veronica, Zhao, Piyu, Chirayil, Sara, Meloni, Gabriele, Sherry, A. Dean
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17-07-2019
• Subjects: Animals; Contrast Media - chemical synthesis; Contrast Media - chemistry; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Copper - analysis; Gadolinium - chemistry; Liver - chemistry; Magnetic Resonance Imaging; Mice; Mice, Inbred C57BL; Molecular Structure; Serum Albumin, Human - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.8b13493

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 r 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 r 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). T 1-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.