Highly Potent MRI Contrast Agent Displaying Outstanding Sensitivity to Zinc Ions

Zinc ions play an important role in numerous crucial biological processes in the human body. The ability to image the function of Zn²⁺ would be a significant asset to biomedical research for monitoring various physiopathologies dependent on its fate. To this end, we developed a novel Gd³⁺ chelate that can selectively recognize Zn²⁺ over other abundant endogenous metal ions and alter its paramagnetic properties. More specifically, this lanthanide chelate displayed an extraordinary increase in longitudinal relaxivity (r₁ ) of over 400 % upon interaction with Zn²⁺ at 7 T and 25 °C, which is the greatest r₁ enhancement observed for any of the metal ion-responsive Gd-based complexes at high magnetic field. A "turn-on" mechanism responsible for these massive changes was confirmed through NMR and luminescence lifetime studies on a ¹³ C-labeled Eu³⁺ analogue. This molecular platform represents a new momentum in developing highly suitable magnetic resonance imaging contrast agents for functional molecular imaging studies of Zn²⁺ .