"It's an iron oxide crystal surrounded with a carbohydrate or 'sugar' coating," Neuwelt said. This coating, called dextran, gives the particle a longer plasma half-life, allowing it to slowly slip through the blood-brain barrier, or BBB, the tightly knit group of cells lining the walls of blood vessels in the brain. The BBB serves as a natural defense system by blocking the entry of foreign substances, including therapeutic agents.

"Anytime there's an injury, it induces inflammation," Neuwelt said. Ferumoxtran-10 is "taken up by inflammatory cells in the brain. You can see them in stroke and MS, you can see them in tumors. Gadolinium is basically the size of a large atom and does not enter cells, while this contrast agent is the size of a small virus and does enter cells."

In addition, ferumoxtran-10 can be detected with an iron stain in the tissue removed by biopsy or surgery, allowing physicians to see it in brain tissue samples under a microscope. "Unlike any other MR contrast agent, you can compare the images from an MR scan with the tissue taken out at surgery," Neuwelt said.

And it's relatively safe when diluted and administered as an infusion, although it can cause an allergic-type reaction when administered too quickly, he said.

Neuwelt says he first learned about iron oxide nanoparticles 11 years ago at a National Institutes of Health conference on new medical imaging techniques. "I heard this talk, and they were using it for liver and lymph nodes and I said to myself, 'Well, we ought to be able use it for the brain as well,'" he recalled.

Soon after, in April 1994, Neuwelt and colleagues published a study in the journal Neurosurgery showing that iron oxide nanoparticles could be delivered across the blood-brain barrier to the brain cells of rats and could be seen with MR.

"Once we realized that iron oxide nanop
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Contact: Jonathan Modie
modiej@ohsu.edu
503-494-8231
Oregon Health & Science University
26-May-2004