A gadolinium(III) complex with 8-amidequinoline based ligand as copper(II) ion responsive contrast agent

A new Cu(2+)-responsive MRI contrast agent (Gd-QDOTAMA) with a quinoline-based ligand was synthesized and characterized. Relaxivity studies on Gd-QDOTAMA showed that the relaxivity increased from 4.27 mM(-1) s(-1) to 7.29 mM(-1) s(-1) in response to equimolar amounts of copper(II) ion, corresponding to ca. 71% relaxivity enhancement. Distinct changes in relaxivity were undetected upon addition of physiologically relevant alkali metal cations (K(+) or Na(+)), alkaline earth metal cations (Mg(2+) or Ca(2+)), or d-block metal cations (Zn(2+), Cu(+), Fe(2+), Fe(3+)), indicating a high selectivity for Cu(2+) over other biologically relevant metal ions. Moreover, the influence of common biological anions at physiological levels on the Cu(2+)-responsive contrast agent was also studied. Luminescence studies on the Eu counterpart Eu-QDOTAMA suggest that the enhancement in relaxivity for Gd-QDOTAMA in response to Cu(2+) is most likely due to the increased number of inner-sphere water molecules around Gd(3+) upon Cu(2+) binding to the 8-amidequinoline moiety. In vitro T(1)-weighted phantom images of Gd-QDOTAMA confirmed that signal intensity was markedly increased by the addition of equimolar amounts of Cu(2+).