This high-resolution transmission electron micrograph of particles made by the research team shows the particles’ highly uniform size and shape. These are iron oxide particles just 3 nm across, coated with a zwitterion layer. Their small size means they can easily be cleared through the kidneys after injection. [Image courtesy MIT researchers]
Gadolinium-based agents cause rare but significant side effects in a small number of patients. In some cases, using gadolinium has been known to cause nephrogenic systemic fibrosis, which can be fatal. Gadolinium is also being investigated by the FDA because it can build up in the brain. The iron oxide nanoparticle agent is designed to replace those agents to provide a safer substitute, according to the new research.
“Over the last decade more and more side effects (from gadolinium) have come to light,” said Oliver Bruns, an MIT research scientist and one of the authors of this research. “None of these issues exist for iron oxide.”
Approximately 60 million MRI procedures are performed annually worldwide to identify specific organs and blood vessels in the body, and about one-third of those procedures use contrast-enhancing agents that have gadolinium.
Contrast agents are injected into a patient during an MRI and are flushed from the body through the kidneys after. They are important for being able to see the fine details of organ structures, blood vessels and other specific tissues in the body. The gadolinium-based contrast agents light up certain areas on an MRI image while other areas remain dark.
In the past, iron oxide particles have been used as a dark or negative contrast agent, but radiologists typically prefer light or positive agents like gadolinium.
The researchers saw that the tiny nanoparticles of iron oxide produced similar MRI contrast to gadolinium when they were treated with a zwitterion coating. The zwitterions are molecules that have both positive and negative electrical charges that end up canceling each other out to make it neutral.
The iron oxide has an inorganic core that is small enough to make a positive contrast MRI. The zwitterions that coat the iron oxide are water soluble, compact and biocompatible. The two of them together have a hydrodynamic diameter of 4.7 nm, which is just under the 5.5-nm renal clearance threshold.
Initial tests of this method demonstrated that the iron oxide particles were effective as contrast agents. The researchers are now tasked with furthering toxicology testing to see how safe the particles are as they work to improve the characteristics of the iron oxide and zwitterions combination.
The University Medical Center Hamburg-Eppendorf, Brown University and Massachusetts General Hospital also participated in the research. The research was funded by the MIT-Harvard NIH Center for Cancer Nanotechnology, the Army Research Office, NIH-funded Laser Biomedical Research Center, MIT Deshpande Center and the European Union Seventh Framework Program. It was published online in the Proceedings of the National Academy of Science journal.
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