MRI Drug May Enhance Chemotherapy

A contrast agent currently used in magnetic resonance imaging (MRI), called mangafodipir, may increase the cancer-killing ability of some chemotherapy drugs while protecting healthy cells, according to a new study.

Many anticancer agents work by raising the levels of tumor cell hydrogen peroxide. Tumor cells are especially sensitive to hydrogen peroxide and die as a result. However, specific enzymes in the body can work to protect cells from this type of damage, rendering certain cancer drugs less effective. Furthermore, the drugs are toxic to normal cells. The drug mangafodipir, a contrast agent administered to patients before they have an MRI scan, helps enhance the production of hydrogen peroxide while at the same time, through different biologic processed, protects healthy cells from the negative effects of oxidative damage.

Jérôme Alexandre, M.D., from the Groupe hospitalier Cochin-Saint Vincent de Paul (Paris, France) and coworkers exposed tumor cells and white blood cells from 10 cancer patients and white blood cells from six control subjects to three chemotherapy drugs--paclitaxel, oxaliplatin, and 5-fluorouracil--in the presence or absence of mangafodipir. They also evaluated the effects of mangafodipir on colon cancer cells in mice treated with paclitaxel.

The authors discovered that mangafodipir protected the white blood cells taken from healthy volunteers and from cancer patients. The agent also protected paclitaxel-treated mice from infection that would cause a lowered white blood cell count and helped increase the cancer cell-killing ability of the chemotherapy drug paclitaxel against the cancer cells in mice.

"Our results support investigation of the use of mangafodipir in cancer patients, because mangafodipir may enhance the therapeutic index of anticancer agents by both protecting normal cells and increasing antitumoral activity of these agents,” the authors wrote in their study, published in the February 15, 2006, issue of the Journal of the National Cancer Institute. "The safety of mangafodipir administered as a contrast agent in magnetic resonance imaging has already been demonstrated.”

In an accompanying editorial, James H. Doroshow, M.D., of the U.S. National Cancer Institute (Bethesda, MD, USA), suggested that clinical trials may be the next approach for studies of drugs such as mangafodipir that affect oxidative stress in tumor cells. He wrote, "Overall, this study contributes to our rapidly developing understanding of tumor cell [oxidation-reduction] balance and to the possibility that therapeutic approaches to the modulation of oxidant-mediated growth control may be possible in the near future, perhaps with mangafodipir or with other [oxidation-reduction] modulators in development.”



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Groupe hospitalier Cochin-Saint Vincent de Paul