title: A cell-permeable gadolinium contrast agent for magnetic resonance imaging of copper in a Menkes disease model.
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-1s-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 cellulorelaxivity measurements andT1-weighted phantom images using a Menkes disease model cell line demonstrate the utility of Arg8CG2 to report on biological perturbations of exchangeable copper pools.
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Que
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: New
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.|Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Chang