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Issue 6, 2012
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A cell-permeable gadolinium contrast agent for magnetic resonance imaging of copper in a Menkes disease model

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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.

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

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Publication details

The article was received on 06 Mar 2012, accepted on 25 Mar 2012 and first published on 18 Apr 2012


Article type: Edge Article
DOI: 10.1039/C2SC20273E
Citation: Chem. Sci., 2012,3, 1829-1834
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    A cell-permeable gadolinium contrast agent for magnetic resonance imaging of copper in a Menkes disease model

    E. L. Que, E. J. New and C. J. Chang, Chem. Sci., 2012, 3, 1829
    DOI: 10.1039/C2SC20273E

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