Gadolinium-based contrast agents (GBCAs) are the only approved class of drugs for use with MRI in the United States.

There has been increasing concern among radiologists about potential legal exposure from its use. Several patients have come forward reporting adverse effects and there have been some high-profile cases, including a recent lawsuit that was dropped by Chuck Norris and his wife, Gena.

For radiologists this begs the questions; should we continue to use gadolinium-based agents? Are we putting ourselves at risk of legal exposure if we do so? Based on the current research, here’s what we know:

What is gadolinium retention?

Gadolinium is the metal found in all GBCAs, which are used as contrast agents for different types of MRI (largely neuro, vascular and liver). It has been found that small amounts of gadolinium may be retained in the body, including the brain, bones, skin and other parts. The period of retention may be months to years.

In a recent 2024 update, the FDA reinforced its 2017 findings that all forms of GBCAs are associated with gadolinium retention. However, the FDA has still found no conclusive evidence of harm caused by this retention. they continue to support ongoing research into the effects of gadolinium retention and have updated guidelines to emphasize caution, especially for certain high-risk groups such as individuals undergoing multiple doses, pregnant women, and young children. 

The FDA’s updated classification indicates:

 –High retention: Omniscan, Optimark

–Moderate retention: Eovist, Magnevist, MultiHance

–Low retention: Dotarem, Gadavist, ProHance 

Reported side effects

Gadolinium-based contrast agents have been used in MRI for over 30 years now. It was in 2016 that the term “gadolinium deposition disease” was first described:

“In 2016, Semelka et al first described a constellation of self-reported symptoms in patients with normal renal function who had received GBCAs. Suggesting causation from correlation, the authors postulated this symptomatology to represent GDD and went on to propose diagnostic criteria for this newly proposed disease. To meet the diagnostic criterion for GDD, a patient must exhibit at least three of the following five broad symptom clusters within a period of hours to 2 months post-GBCA administration: (1) peripheral neuropathic pain in either a “glove and stocking” or generalized distribution; (2) joint stiffness, muscle spasms, buzzing sensation, and fatigue; (3) headache; (4) clouded mentation; and (5) distal extremity and skin substrate thickening, discoloration, and pain. Furthermore, it was proposed that GDD may clinically manifest after the initial infusion of GBCA or after multiple administrations in a dose-dependent manner.”

At this stage, GDD is still a proposed disease with further research being undertaken, however, since the disease was proposed, there has been a rash of lawsuits from patients who feel that they meet the criteria for the disease.

While FDA’s official position is still that GDD cannot be proven (or disproven) yet, they now require imaging centers to distribute literature informing patients of potential gadolinium risk. The European Medicines Agency went further by restricting the use of certain types of GBCAs.

There is significant confusion for both medical practitioners and patients because while regulatory bodies have issued these requirements, they’ve at the same time convened regulatory scientific panels who have made statements of “no causality.”

Current insights

While GDD is still a proposed disease under investigation, there has been an increate in lawsuits from patients who believe they meet the criteria for GDD. The FDA’s position remains that GDD cannot yet be proven or disproven, but they now require imaging centers to distribute updated literature to inform patients of potential gadolinium risks. The European Medicines Agency has taken more stringent measures by restricting the use of certain GCAs. 

What can imaging centers do?

Radiologists are concerned that precautionary measures may be misconstructed as acknowledgement as causation, creating an environment ripe for legal exposure. Here are some tips to help understand the cautions:

 –Understand the Risks: Nephrogenic systemic fibrosis (NSF) is the only proven disease linked to GBCAs, affecting patients with impaired renal function. The FDA has mandated black box warnings and advised caution for these patients. There are no known harmful effects in patients with normal renal function. 

–Educate Patients: Provide updated literature and discuss the risks and benefits of GBCAs with patients. Weigh the potential side effects against the necessity of obtaining a clear MRI image for accurate diagnosis. 

–Select the Appropriate Agent: Familiarize yourself with the different types of GBCAs and their retention profiles. Opt for macrocyclic GBCAs (Dotarem, Gadavist, ProHance) that are associated with lower retention levels. Specifically, Gadoteridol is linked with the least gadolinium retention in the brain.

–Stay Informed: Keep up with the latest research and data on gadolinium and its potential side effects. Implement practices that minimize the risk of retention whenever possible. 

We still await more data and research on any side effects of gadolinium retention, so perhaps an approach that looks to apply the least risk of retention first is a good step. Here’s a thought to conclude from a recent RSNA annual meeting:

“This is a nice time for radiologists to become more active in the decision-making about how these (agents) are chosen,” said H. Benjamin Harvey, MD, a neuroradiologist at Massachusetts General Hospital in Boston and assistant professor of radiology at Harvard Medical School. “My opinion is at this point, there’s too much industry thought; there’s too much marketing influence and there’s too many side deals that might be leading to one being chosen over another, not a data-driven approach.”