A Bioinspired Cu2+-Responsive Magnetic Resonance Imaging Contrast Agent with Unprecedented Turn-On Response and Selectivity

Abstract

Imaging extracellular Cu2+ in vivo is of paramount interest due to its biological importance in both physiological and pathological states. Magnetic resonance imaging (MRI) is a powerful technique to do so. However, the development of efficient MRI contrast agents selective for Cu2+, particularly versus the more abundant Zn2+ ions, is highly challenging. We present here an innovative Cu2+-responsive MRI contrast agent that contains a bioinspired Cu2+ binding site. This sensor shows a remarkable increase in relaxivity of nearly 400% in the presence of Cu2+, which could be rationalized in terms of an increase in the hydration number of the Ln3+ ion, as demonstrated by spectroscopic and relaxometric studies and supported by density functional theory calculations. Importantly, the system also shows an unprecedented selectivity for Cu2+, in particular over Zn2+. Phantom MRI images were recorded at 9.4 T to highlight the potential of such probes, which lies directly in their bioinspired design.