Gadolinium contrast agents - are they really safe?

Gadolinium-based contrast agents (GBCA) are used worldwide for enhanced MRI examinations, including heart and vessels. Gadolinium is a highly toxic heavy metal. If used in GBCA it must be tightly bound to ligands. The configuration of ligands influences the stability of the GBCA and two types of chelates have been used. Macrocyclic chelates offer better protection and binding of gadolinium ion than linear chelates with a flexible open chain - gadolinium could be more easily released from the latter ones. GBCAs are excreted from the body mostly by the kidneys, which is of importance in chronic kidney disease. Two states are related to gadolinium: nephrogenic systemic fibrosis (NSF) and gadolinium body storage. NSF is a severe and debilitating disease, directly connected to gadolinium toxicity, proven after the use of linear chelates. Due to strict recommendations of radiology societies, NSF was practically eradicated. Gadolinium deposition was observed especially in bones and in some brain areas: in dentate nucleus and in globus pallidus, even years after the GBCA administration. The form of the storage (chelated or free), as well as their clinical impact, are not clear, but first observations of "gadolinium deposition disease" have been reported.