Design of gadolinium complexes as magnetic resonance imaging contrast agents

Gadolinium chelates have become an indispensable tool for the production of contrast enhanced MRI since their introduction into the clinic. A number of gadolinium contrast agents (GdCAs) have been successfully translated into the clinic, however recently some of these have been restricted due to safety concerns. The macrocyclic GdCAs have been shown to be highly stable and have a good safety record; this GdCA design provides a template for the development of new agents with higher relaxivity. This chapter explores the important design considerations for the production of high relaxivity, high stability GdCAs and examines some recent examples that have undergone clinical trials. These examples focus on different methods of increasing the molecular weight of the GdCA to slow tumbling in solution, which improves relaxivity whilst retaining the high stability chelate core. The incorporation of hydrophilic arms that further increase the molecular weight of the GdCA through association of water molecules has been shown to be effective in this goal and does not significantly impact upon the biodistribution of the GdCA.