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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

1
Department of Chemistry, University of California, Berkeley, California 94720, USA.
2
Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
#
Contributed equally

Abstract

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.

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