Current advancement in the development of manganese complexes as magnetic resonance imaging probes

Emerging non-invasive molecular imaging modalities can detect a pathophysiological state at the molecular level before any anatomic changes are observed. Magnetic resonance imaging (MRI) is preferred over other nuclear imaging techniques owing to its radiation-free approach. Conventionally, most MRI contrast agents employed predominantly involve lanthanide metal: Gadolinium (Gd) until the discovery of associated severe nephrogenic toxicity issues. This limitation led a way to the development of manganese-based contrast agents which offer similar positive contrast enhancement capability. A vast quantity of experimental data has been accumulated over the last decade to define the physicochemical characteristics of manganese chelates with various ligand scaffolds. One can now observe how the ligand configurations, rigidity, and donor-acceptor characteristics impact the stability of the complex. This review covers the current trends in the development of manganese-based MRI contrast agents, the mechanisms they are based on and design considerations for newer manganese-based contrast agents with higher diagnostic strength along with better safety profiles.