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

J Am Chem Soc. 2019 Jul 17;141(28):11009-11018. doi: 10.1021/jacs.8b13493. Epub 2019 Jul 3.

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 r1 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 r1 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). 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's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Contrast Media
  • Coordination Complexes
  • Copper
  • Gadolinium
  • Serum Albumin, Human