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ShareMay 13, 1999 — HOUSTON, May 12, 1999 -- Rice University researchers recently conducted the first detailed biological study showing what happens to carbon fullerene material--the buckyball and its relatives--in mice, proving that fullerenes with radioactive metals inside can be cleared from the body and that they are attracted to bone.
The find gives promise to developing fullerenes--hollow, cagelike carbon molecules discovered at Rice in 1985--for use in medical applications such as nuclear medicine, magnetic resonance imaging (MRI) and drug delivery.
Using a rugby-shaped ball of a C82 fullerene containing radioactive holmium atoms, Rice chemist Lon Wilson and graduate student Dawson Cagle created a radiotracer similar to those that doctors use to image patients' diseased organs or kill cancerous tumors. They injected the material into mice and rats and observed where it went, how long it stayed there and how it cleared from the body.
Research collaborators include Michael Alford of TDA Research Inc. in Wheat Ridge, Colo., Stephen Kennel and Saed Mirzadeh at the Oak Ridge National Laboratory in Oak Ridge, Tenn., and Gary Ehrhardt of the University of Missouri.
Their results were published in the April 27 issue of the Proceedings of the National Academy of Sciences.
"This work shows that fullerene materials can be engineered to do their work and be cleared from the body," Wilson says. The material cleared from the blood, it was not toxic, and it was specifically attracted to bone tissue. These qualities make fullerenes and metallofullerenes worth pursuing as new medical materials, Wilson and Cagle say.
The researchers made the fullerene material water soluble by putting hydroxy chemical groups on the surface of the metallofullerenes to make them resemble "stealth liposomes," which are materials invisible to the immune system.
The Rice chemists saw clearance of about 20 percent of the material over a five-day period in rats. The next step will be to pursue methods to improve upon the clearance. "The door is now open to see how well we can encourage clearance as well as the targeting of specific tissue," Wilson says.
Theirs is the first detailed study of metallofullerenes in animals, studying distribution of the material in mice and its metabolism in rats.
Wilson and Cagle showed that radioactive fullerenes stay in the blood for over an hour, an advantage for imaging the circulatory system. They also showed that the material localizes in the spleen, kidneys and liver, but with slow and steady clearance.
The metallofullerenes showed slow clearance from all tissue except bone, where it steadily increased with time, a totally unexpected result, according to Wilson. Says Cagle, "In theory, it is possible that we could selectively target bone tissue for delivery of drugs, for instance, to treat leukemia, bone cancer and bone pain."
An advantage of a metallofullerene is that the radioactive metal is trapped inside the carbon shell, which is very stable and resistant to metabolism by the body. Wilson suspects that the fullerene cages remain intact throughout the process and do not release toxic metals in the body.
Materials currently used can break down after an hour and some amount of their toxic metals can be released into the body.
Wilson notes: "Commercial development of fullerene products has been hampered by the cost of fullerenes, but medical applications will tolerate higher cost, especially for unique benefits when only very small amounts of material are needed per dose. We are very encouraged by our early results and believe that fullerene materials could be the basis of many new designer drugs of the 21st century."
This research was funded by the National Institutes of Health.
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