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A primer for imaging leaders on controversial GBCAs

June 26, 2017

    Gadolinium-based contrast agents (GBCAs), first approved by the U.S. Food and Drug Administration (FDA) in 1988, have become the go-to contrast agent for MRI exams in recent years. In fact, roughly one in every three MRI exams now uses GBCAs to improve the clarity of the body's internal structure. Such frequent usage is a testament to the benefits that GBCAs provide to radiologists' diagnostic capabilities. 

    Gadolinium deposition: A controversy years in the making

    While the diagnostic usefulness of GBCAs over the past 30 years has rarely been questioned, the safety of GBCAs is a different story. In 2006, researchers found that the administration of GBCAs could lead to nephrogenic systemic fibrosis (NSF) in patients with renal failure. This discovery led the industry to shift toward more stable versions of GBCAs and limiting the use of GBCAs in patients with renal failure.

    However, despite the industry shift, recent studies recently have showed gadolinium deposition in the brain, even for patients with normal renal functions. The studies, published in 2014, prompted further reviews of the potential risks of GBCAs, including one by FDA, which announced it was investigating GBCAs in July of 2015.

    Then, in March of this year, the European Medicines Agency (EMA) recommended that four GBCAs be pulled from the market. Those GBCAs were characterized by their linear molecular structure, which can make them more likely to release gadolinium. EMA made no changes to its recommendations for the remaining GBCAs, as these utilize a macrocyclic structure that is less likely to lead to gadolinium deposits. Many in the radiology world disagreed with EMA's decision, citing the benefits of GBCAs as too important to ban without a clear understanding of the effects of gadolinium deposits.

    In fact, just last month, on May 22, FDA moved in the opposite direction, announcing that "restricting GBCA use is not warranted at this time." FDA is basing its announcement on its two-year review of GBCAs, which "has not identified adverse health effects from gadolinium retained in the brain." Meanwhile, EMA is now further investigating GBCAs and may revise its ruling at the end of this review, which is expected to conclude in July.

    Guidance in an uncertain world

    The contradicting recommendations from EMA and FDA around the use of GBCAs highlight our lack of knowledge on gadolinium deposits. As this debate continues, imaging leaders should avoid taking a stand in either extreme.

    Imaging leaders should not completely dismiss gadolinium concerns while the effects of these deposits remain unknown. However, avoiding GBCA administration when clinically necessary could directly impact patient care. Therefore, radiologists should take a measured approach with gadolinium and ensure that every use of gadolinium is clinically necessary.

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