Distribution map of gadolinium deposition within the cerebellum following GBCA administration

Gadolinium-based contrast agents (GBCAs) are an essential tool in clinical MRI. Millions of doses are administered annually to patients worldwide.1 However, free gadolinium, the basis of GBCAs, is extremely toxic in only small amounts. Gadolinium has an atomic radius similar to that of calcium and can interfere with calcium-dependent processes such as voltage-gated calcium channels or calcium-activated enzymes.1 To reduce toxicity, GBCAs are composed of gadolinium in chelated form. Following GBCA administration, presumably the gadolinium–chelate complex is excreted intact by the kidneys in patients with normal renal function. Each of the 9 Food and Drug Administration–approved MRI contrast agents has its own specific chelate, leading to variation in stabilities of the gadolinium–chelate complex. GBCAs are generally classified as either linear or macrocyclic based on chelate structure. An ionic, macrocyclic structure has the highest kinetic and thermodynamic stabilities.1