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 μM Zn²⁺ in the presence of HSA by MRI in vitro, a value slightly more than the total Zn²⁺ concentration in blood (∼20 μM). 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⁺.