Macrocyclic contrast agents used in MRI have high kinetic stability

All MRI contrast agents currently marketed in Canada contain gadolinium. Gadolinium is used because of its paramagnetic properties, which accelerates the magnetic relaxation of water protons, providing contrast enhancement in a T1-weighted image. Unchelated gadolinium can be toxic to biological systems, depending on the dose, so it is important that it is chelated with a ligand to reduce its potential toxicity.¹

There are two distinct structures of gadolinium-based contrast agents (GBCAs) available on the market: the linear agents and the macrocyclic agents.¹ Linear agents have an open flexible chain, whereas the macrocyclic agents have a rigid structure with a pre-organized cavity that fits the gadolinium ion inside, reducing the probability of gadolinium release.

When injected into the body, the GBCA will encounter a variety of competitors that may interact with the gadolinium ion or with the ligand. Metal ions, such as zinc, may displace the gadolinium from its chelate through a process called transmetallation. In a study that compared the stabilities of different MRI contrast agents, linear and macrocyclic agents were observed under physiological conditions, in human serum at pH 7.4 and 37°C, for 15 days. At the end of the 15 days, the percent of gadolinium release observed from the multi-purpose linear nonionic and ionic agents was approximately 20% and 2%, respectively, while all macrocyclic agents remained stable with no detectable release of gadolinium (limit of quantification 0.1%).¹

These results demonstrate the high kinetic stability of the macrocyclic agents, which makes them essentially inert.

See video below where this difference between the stability of linear and macrocyclic agents is demonstrated.