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OHSU, VAMC Researchers Reveal Benefits of Tiny Iron Particles in Brain Tumor Imaging

   Portland, Ore.

Iron oxide particles called ferumoxtran may also be a useful tool for tumor pathology and gene therapy research

Researchers at Oregon Health & Science University and Portland Veterans Affairs Medical Center have discovered that ultra small iron oxide particles may help improve brain tumor imaging methods. When introduced into the blood stream, these particles have the ability to help define the form of brain tumors for extended periods of time when used in conjunction with magnetic resonance imaging (MRI). In the future the use of these specially coated particles called ferumoxtran could allow neurosurgeons to better track the progress of brain tumor removal throughout the operation. Ferumoxtran also offers promising advancements in the fields of pathology and genetic therapy research. The research appears as the cover article in the April issue of the American Journal of Neuroradiology.

Currently a compound called gadolinium is the standard "contrast agent" introduced intravenously into the brain in order to distinguish brain tumors from normal brain material when viewing an MRI. However, gadolinium has its shortcomings. It only works for 30 to 60 minutes before its effects dissipate. In addition, gadolinium can sometimes highlight brain material that is not diseased, but merely traumatized during surgery.

In comparison, ferumoxtran particles highlight the area around the tumor, not traumatized tissue. The particles also take much more time to dissipate from the blood stream. This research showed the presence of ferumoxtran in images taken 24 hours after its infusion. This is made possible through a special glucose coating called dextran which keeps the ferumoxtran from disappearing prematurely. In fact, in previous studies using rat models, researchers found that due to this coating, ferumoxtran has the ability to remain in the brain for weeks after direct brain injection before disappearing.

"Within the next few weeks, OHSU will be one of the only hospitals in the entire country with a neurosurgery suite outfitted with an MRI machine. With the use of ferumoxtran, surgeons using MRI-outfitted surgical suites might have the ability to image a tumor in the brain during the operation without repeated introduction of a contrasting agent," said senior author Edward A. Neuwelt, M.D., Portland VA Medical Center neurosurgeon and OHSU School of Medicine professor of neurology and neurosurgery.

Lead author Peter Varallyay, M.D., Neuwelt and their colleagues said that in addition to the possible future benefits in the operating room, ferumoxtran may play a major role in the pathology lab. Ferumoxtran particles can be tracked as they circulate through the body. This makes it possible for pathologists to directly compare sections of diseased tissue removed from the brain and stained to reveal these iron particles with preoperative MRI images to better understand the form and function of the tumor.

The ability to track ferumoxtran in the body may also benefit gene therapy research. The iron particles, which are the size of a small virus, could help determine the effectiveness of using certain viruses as vehicles to deliver therapeutic genes to areas of the human body. By tracking distribution of ferumoxtran particles, scientists would have the ability to pinpoint where these viral vectors go and whether they are reaching their targets. Using this information, scientists could then use these targeted viruses to carry therapeutic genes. This work has already begun in animal models.

Researchers at OHSU are planning future research into the possible benefits of ferumoxtran as a contrast agent for other neurological diseases that involve lesions. Those diseases include multiple sclerosis, Alzheimer's disease and stroke.

In addition to Neuwelt and Varallyay, co-authors of the AJNR paper include Gary Nesbit, M.D., Leslie L. Muldoon, Ph.D., Randal R. Nixon, M.D., Johnny Delashaw, M.D., James I. Cohen, M.D., Annie Petrillo, F.N.P., and Doris Rink, F.N.P. The Department of Veterans Affairs and the National Institutes of Health supported their work.

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