Daily Bulletin 2015

Contrast Agent Ferumoxytol Safe for MR Imaging in Children

Thursday, Dec. 03, 2015

In the largest study of its kind, researchers have found that ferumoxytol is safe to use as an MR contrast agent in children, according to a presentation Wednesday. The findings are critical for the development of new ferumoxytol-based MR imaging techniques with better image quality and less toxicity, researchers said.

Anne Muehe, M.D.

Anne Muehe, M.D.

Contrast studies with MRI are often performed with gadolinium-based agents, but concerns persist about the toxic gadolinium ion's retention in the body. Recent studies found gadolinium deposition in the brains of people with normal kidney function, raising concern about potential long-term effects, especially in the pediatric population, said study author Anne Muehe, M.D.

"The pediatric population is particularly vulnerable as they are still growing and we really don't know the effects of gadolinium in growing organisms," she said.

Dr. Muehe, a postdoctoral fellow in the laboratory of Heike E. Daldrup-Link, M.D., associate professor of radiology at Stanford Medicine in Stanford, Calif., recently assessed the safety profile of ferumoxytol as an intravenous MRI contrast agent in pediatric patients. Ferumoxytol is approved by the U.S. Food and Drug Administration (FDA) as a treatment for anemia.

"Ferumoxytol is not excreted through the kidneys like gadolinium," said Dr. Muehe. "Instead, it's taken up by bone marrow, liver and spleen, where it is utilized by the body to produce red blood cells."

For the collaborative study between researchers at Stanford's Lucile Packard Children's Hospital and Oregon Health Sciences University, Dr. Muehe, Dan Feng, Ph.D., a medical student at Stanford, and colleagues enrolled 49 pediatric patients, ages five to 18, between September 2009 and February 2015. The patients received either a single dose of ferumoxytol or two to four doses of ferumoxytol at a lower iron concentration, and the researchers observed them closely for adverse events.

"Iron can cause hypotension, so we followed a rigorous protocol and monitored the patients' blood pressure after contrast injection to see if there were any changes," said Dr. Daldrup-Link, co-author of the study. "Building on decades of experience with the clinical use of iron oxide nanoparticles in Europe, we actually obtained the exact safety parameters, which the FDA recommended to users recently."

Out of 65 ferumoxytol injections in 49 pediatric patients, the researchers observed only one episode of an immediate adverse event: a case of nausea. Evaluation of vital signs revealed two episodes of mild hypotension without related clinical signs or symptoms.

"Two patients had drops in blood pressure but had concomitant sedation because they were so young," Dr. Muehe said. "After the sedation wore off, their blood pressure returned to normal."

Analysis of weekly blood tests within one month of injection revealed no significant changes in the patients' kidney or liver function.

Anne Muehe, M.D. consults with a young patient

Anne Muehe, M.D. consults with a young patient.
Photo credit: Edwin Leon

"The results confirmed our hypothesis that ferumoxytol is generally safe as a contrast agent in children," said Dr. Muehe. "Larger prospective studies are needed to determine the incidence and frequency of severe anaphylactic reactions in comparison to traditional gadolinium-based contrast agents."

Dr. Muehe's work on ferumoxytol won her a 2015 RSNA Trainee Research Prize—the same prize that Dr. Daldrup-Link won in the late 1990s after she finished a fellowship at the University of California, San Francisco. Like Dr. Muehe, Dr. Daldrup-Link traveled to the United States from Germany to become a physician-scientist.

"The research prize is a wonderful way to recognize the work of these young people," Dr. Daldrup-Link said. "Positive feedback and encouragement are extremely powerful ways to seed excitement for research and create better imaging technologies for our patients."

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The RSNA 2015 Daily Bulletin is owned and published by the Radiological Society of North America, Inc., 820 Jorie Blvd., Oak Brook, IL 60523.