On March 10, 2017, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) formally submitted its recommendation to suspend use of some linear gadolinium-based contrast agents (GBCAs) due to the potential risk of gadolinium accumulation within humans. As an organization committed to the highest standards in patient care and safety, the American College of Radiology (ACR) closely follows this evolving and controversial topic. After extensive review of the PRAC position and voluminous other materials, the ACR Committee on Drugs and Contrast Media disagrees with the PRAC recommendation.

Although intracranial gadolinium retention following intravenous GBCA administration has only recently been reported, it has been known for over 10 years that some gadolinium chelates are not completely stable in vivo. Fortunately, there is indisputable evidence that the amount of gadolinium deposited in tissues after a single GBCA dose is incredibly small and is detectable using only the most sensitive of medical and scientific instrumentation. Further, although gadolinium accumulation appears to be dose-dependent, there remains no evidence of cellular toxicity, nor is there credible evidence of neurologic sequelae after over 300 million worldwide human doses.

While less sensitive studies that rely upon visually observable changes in T1-weighted MRI signal do not suggest macrocyclic agents deposit gadolinium within brain tissues, more quantitative mass spectrometry data from multiple sources have confirmed that they do, albeit at lower levels. Further, other studies using mass spectrometry have revealed that gadolinium deposition rates for linear and macrocyclic agents vary within a given class, and that different chemical forms of gadolinium (i.e. different gadolinium complexes) appear to be depositing within tissues, some of which would be undetectable using MRI. Therefore, although MRI signal changes led to the observation that gadolinium was being deposited in the brain, they are less reliable for determining the quantity of gadolinium deposition in general. This is particularly true for gadolinium species that are not detectable with MRI and for lower concentrations of retained gadolinium.

The ACR continues to endorse the need for additional research efforts directed towards greater understanding of the mechanisms, cellular effects, and clinical consequences of gadolinium tissue deposition. At this time, there is no compelling evidence that any GBCAs, including linear ones, pose any safety risk with respect to brain deposition of gadolinium. Further, linear agents have significant and well-documented diagnostic utility, and in some instances may have more desirable pharmacologic properties or a lower acute reaction risk than macrocyclic agents.

For further information, interested parties are referred to the ACR-ASNR statement on gadolinium deposition for additional information.

One source for this statement is the ACR Manual on Contrast Media.