Send to

Choose Destination
Chem Sci. 2012 Jun 1;3(6):1829-1834. doi: 10.1039/C2SC20273E. Epub 2012 Apr 18.

A cell-permeable gadolinium contrast agent for magnetic resonance imaging of copper in a Menkes disease model.

Author information

Department of Chemistry, University of California, Berkeley, California 94720, USA.
Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
Contributed equally


We present the synthesis and characterization of octaarginine-conjugated Copper-Gad-2 (Arg8CG2), a new copper-responsive magnetic resonance imaging (MRI) contrast agent that combines a Gd3+-DO3A scaffold with a thioether-rich receptor for copper recognition. The inclusion of a polyarginine appendage leads to a marked increase in cellular uptake compared to previously reported MRI-based copper sensors of the CG family. Arg8CG2 exhibits a 220% increase in relaxivity (r1 = 3.9 to 12.5 mM-1 s-1) upon 1 : 1 binding with Cu+, with a highly selective response to Cu+ over other biologically relevant metal ions. Moreover, Arg8CG2 accumulates in cells at nine-fold greater concentrations than the parent CG2 lacking the polyarginine functionality and is retained well in the cell after washing. In cellulo relaxivity measurements and T1-weighted phantom images using a Menkes disease model cell line demonstrate the utility of Arg8CG2 to report on biological perturbations of exchangeable copper pools.

Supplemental Content

Full text links

Icon for Royal Society of Chemistry Icon for PubMed Central
Loading ...
Support Center