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

摘要

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 vitroT_1-weighted phantom images of Gd-QDOTAMA confirmed that signal intensity was markedly increased by the addition of equimolar amounts of Cu ~(2+).