A New Gadolinium-Based MRI Zinc Sensor

The properties of a novel Gd3+-based MRI zinc sensor are reported. Unlike previously reported Gd3+-based MRI contrast agents, this agent (GdL) differs in that the agent alone binds only weakly with human serum albumin (HSA), while the 1:2 GdL:Zn2+ ternary complex binds strongly to HSA resulting in a substantial, 3-fold increase in water proton relaxivity. The GdL complex is shown to have a relatively strong binding affinity for Zn2+ (K-D = 33.6 nM), similar to the affinity of the Zn2+ ion with HSA alone. The agent detects as little as 30 mu M Zn2+ in the presence of HSA by MRI in vitro, a value slightly more than the total Zn2+ concentration in blood (similar to 20 mu M). This combination of binding affinity constants and the high relaxivity of the agent when bound to HSA suggests that this new agent may be useful for detection of free Zn2+ ions in vivo without disrupting other important biological processes involving Zn2+.