The Rise of Off-Label Iron-Based Agents in Magnetic Resonance Imaging

Gadolinium-based contrast agents (GBCAs) used in MRI have come under fire due to concerns about nephrogenic systemic fibrosis (NSF) and gadolinium retention. These concerns have prompted a search for alternatives to GBCAs. One attractive candidate is superparamagnetic iron oxide (SPIO). Over the past 20 years, several SPIO agents have been developed and approved for niche clinical applications in MRI. One interesting SPIO agent is ferumoxytol (Feraheme^®), an FDA-approved intravenous medication used to treat iron-deficiency anemia in patients with chronic kidney disease. In preliminary studies examining its off-label use as an intravenous contrast agent, ferumoxytol appeared promising for MRI and MR angiography. However, experience with this agent remains limited. One key benefit of ferumoxytol is that it carries no risk of NSF in patients with impaired renal function. On the other hand, ferumoxytol has been reported to cause severe adverse events, including hypotension, hypersensitivity reactions, anaphylaxis, and death. Moreover, the rate of such events has been substantially greater than those observed with GBCAs or nonionic iodinated contrast media. In response to these data, the FDA issued a black box warning for ferumoxytol in 2015. To ensure patient safety, hospitals and imaging facilities must develop a plan to train MRI personnel to recognize and manage adverse reactions to ferumoxytol. Another challenge of using ferumoxytol concerns its pharmacokinetics and biodistribution, which differ from those of GBCAs. These differences can lead to unexpected patterns or persistence of tissue enhancement on MRI. In particular, ferumoxytol can remain in the body for days, weeks, or months after intravenous administration, potentially causing an unsuspecting radiologist to misinterpret an MRI. The decision to use ferumoxytol for a specific patient and clinical indication requires the radiologists to carefully weigh risk-benefit tradeoffs and consider alternative diagnostic tests.