Chapter 343 - Lanthanide-based responsive MRI contrast agents

Abstract

Magnetic Resonance Imaging (MRI) has become an indispensable technique in modern medicine, and Gd3+-based contrast agents are invaluable tools for the enhancement of MRI image quality. Molecular imaging applications have also spectacularly developed in the last decades, though they remain so far restricted to preclinical imaging. In parallel, the chemical design of lanthanide-based responsive imaging agents which provide an MRI-detectable response to specific biomarkers has attracted much interest. Interaction with biologically relevant molecules can promote changes in the structure, and correspondingly in the magnetic properties of a lanthanide complex in multiple ways, and this opens unlimited opportunities to create responsive probes. An increasing number of these novel imaging probes have proved to be applicable in biologically relevant in vivo experiments. Nevertheless, in such complex environments, the control of all parameters that are responsible of the biomarker-dependent MRI changes is often difficult, and the correlation between in vitro mechanistic understanding and in vivo data is not always obvious. In this review, we intend to illustrate, via a selection of representative examples, the different design strategies which are at the disposal of a chemist to generate a biomarker-dependent response in MRI, based on 1H relaxation, paramagnetic chemical exchange saturation transfer (ParaCEST), paramagnetic shift (Parashift) or 19F detection. Within this vast research field, we decided to focus only on the visualization of two classes of biomarkers: endogenous metal ions and enzymatic activities.