Metal-based redox-responsive MRI contrast agents

•Metal-based complexes can provide relaxation and paraCEST redox responsive probes.•Some ligand-based and metal-based T1 and paraCEST redox probes work in small animals.•Mn-based nanoparticles - have a strong redox-active relaxation response in animals.•Ratiometric methods can provide quantitative redox evaluation of cells in vitro. Given their potential in a better characterization and diagnosis of major pathologies like cancer or chronic inflammation, redox-activated Magnetic Resonance Imaging (MRI) probes have recently attracted much interest from chemists. Such redox responsive probes are capable of reporting on specific biomarkers that are related to tissue redox potential disruption or hypoxia. Lately, this research area has experienced remarkable development, including redox-responsive metal complexes and nanoparticles. Here we critically review the progress with a specific focus on metal-based probes and some nanoparticle examples. We demonstrate, via representative cases, the different molecular mechanisms that can generate a redox-modulated MRI response. They can be based on the redox activity of either the ligand or the metal center, provided the different oxidation states of the metal ion are endowed with different magnetic properties. A particular emphasis is given to recent advances and to the imaging probes that have attained in vivo validation. In overall, we aim to provide the reader with a comprehensive view of how intracellular or extracellular redox buffer systems can be assessed by using MRI contrast agents based on lanthanide or transition metal ions using T1-weighted, T2-weighted, paraCEST 1H or 19F MRI.