Safety of the Gadolinium-Based Contrast Agents for Magnetic Resonance Imaging, Focusing in Part on Their Accumulation in the Brain and Especially the Dentate Nucleus.

The established class of intravenous contrast media for magnetic resonance imaging is the gadolinium chelates, more generally referred to as the gadolinium-based contrast agents (GBCAs). These can be differentiated on the basis of stability in vivo, with safety and tolerability of the GBCAs dependent upon chemical and biologic inertness. This review discusses first the background in terms of development of these agents and safety discussions therein, and second their relative stability based both on in vitro studies and clinical observations before and including the advent of nephrogenic systemic fibrosis. This sets the stage for the subsequent focus of the review, the current knowledge regarding accumulation of gadolinium in the brain and specifically the dentate nucleus after intravenous administration of the GBCAs and differentiation among agents on this basis. The information available to date, from the initial conception of these agents in 1981 to the latest reports concerning safety, demonstrates a significant difference between the macrocyclic and linear chelates. The review concludes with a discussion of the predictable future, which includes, importantly, a reassessment of the use of the linear GBCAs or a subset thereof.