Update on Gadolinium Based Contrast Agent Safety, From the AJR Special Series on Contrast Media.

Since its introduction 35 years ago, gadolinium-enhanced MRI has fundamentally changed medical practice. While extraordinarily safe, gadolinium-based contrast agents (GBCAs) may have side effects. Four distinct safety considerations include: acute allergic-like reactions, nephrogenic systemic fibrosis (NSF), gadolinium deposition, and symptoms associated with gadolinium exposure. Acute reactions after GBCA administration are uncommon-far less than with iodinated contrast agents-and, while rare, serious reactions can occur. NSF is a rare, but serious, scleroderma-like condition occurring in patients with kidney failure after exposure to American College of Radiology (ACR) Group 1 GBCAs. Group 2 and 3 GBCAs are considered lower risk, and, through their use, NSF has largely been eliminated. Unrelated to NSF, retention of trace amounts of gadolinium in the brain and other organs has been recognized for over a decade. Deposition occurs with all agents, although linear agents appear to deposit more than macrocyclic agents. Importantly, to date, no data demonstrate any adverse biologic or clinical effects from gadolinium deposition, even with normal kidney function. This article summarizes the latest safety evidence of commercially available GBCAs with a focus on new agents, discusses updates to the ACR NSF GBCA safety classification, and describes approaches for strengthening the evidence needed for regulatory decisions.