MRI contrast agents: Basic chemistry and safety

Magnetic resonance imaging (MRI) contrast agents are pharmaceuticals used widely in MRI examinations. Gadolinium-based MRI contrast agents (GBCAs) are by far the most commonly used. To date, nine GBCAs have been commercialized for clinical use, primarily indicated in the central nervous system, vasculature, and whole body. GBCAs primarily lower the T(1) in vivo to create higher signal in T(1)-weighted MRI scans where GBCAs are concentrated. GBCAs are unique among pharmaceuticals, being water proton relaxation catalysts whose effectiveness is characterized by a rate constant known as relaxivity. The relaxivity of each GBCAs depends on a variety of factors that are discussed in terms of both the existing agents and future molecular imaging agents under study by current researchers. Current GBCAs can be divided into four different structural types (macrocyclic, linear, ionic, and nonionic) based on the chemistry of the chelating ligands whose primary purpose is to protect the body from dissociation of the relatively toxic Gd(3+) ion from the ligand. This article discusses how the chemical structure influences inherent and in vivo stability toward dissociation, and how it affects important formulation properties. Although GBCAs have a lower rate of serious adverse events than iodinated contrast agents, they still present some risk.