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  • Research into Radiotherapy Technique Forecasts Future of Noninvasive Brain Cancer Treatment

    John Morgan, Science Writer, UW Madison Synchrotron Radiation Center

    January 2, 2006

    With an equal rate of incidence and mortality-the number of those who get it, and the number of those who die from it-Glioblastoma Multiforme (GBM) is a brain cancer death sentence. Of the approximately 12,000 people who are diagnosed with GBM annually in the U.S., half will die within a year, and the rest within 3 years. Currently, the only treatments that stretch survival to its limits are exceptionally invasive surgeries to remove the tumor and radiation treatment with the maximum tolerated dose-all leading to a painfully low quality of life. Because of this, researchers are racing to find the answers to cure or at least slow down GBM.

    Gelsomina "pupa" De StasioIn an article in the January 1, 2006 issue of the journal Clinical Cancer Research, Gelsomina "pupa" De Stasio, professor of physics at UW Madison, and her colleagues report on their exciting research into using a new radiotherapy technique for fighting GBM with gadolinium-an approach that might some day lead to not only a much less invasive treatment of this disease, but possibly a cure.

    "It's the most lethal cancer there is. The only good thing about it is that, if left untreated, death is relatively quick and pain-free, since this tumor does not form painful metastases in other parts of the body."

    The therapy, called Gadolinium Synchrotron Stereotactic Radiotherapy (GdSSR), requires a gadolinium compound to find tumor cells and penetrate them, down into their nuclei, while sparing the normal brain. Then, the patient's head isGlioblastoma Cancer Cells irradiated with x-rays. For these x-ray photons the whole brain is transparent, while gadolinium is opaque. Then, where gadolinium is localized-in the nuclei of the cancer cells only-what's known as the photoelectric effect takes place.

    "Exactly 100 years after Einstein first explained this effect, we have found a way to make it useful in medicine. In this effect atoms absorb photons and emit electrons. The emitted electrons are very destructive for DNA, but have a very short range of action. Therefore to induce DNA damage that the cancer cells cannot repair, and consequently cell death, gadolinium atoms must be localized in the nuclei of cancer cells," De Stasio explains. "Furthermore, two other conditions must be satisfied: gadolinium must be absent from normal cells, and must be present in the majority of the cancer cell nuclei. The first condition is well demonstrated by MRI, while the second was recently demonstrated using synchrotron spectromicroscopy."

    De Stasio, the first to introduce this technique into the biological and medical fields, is working to develop the therapy to treat and perhaps cure GBM. In the current article, she and her colleagues prove that gadolinium reaches more than 90% of the cancer cell nuclei, using 4 different kinds of human glioblastoma cells in culture.

    "We know Gd targets the tumor and with spectromicroscopy and high resolution subcellular analysis we can prove that gadolinium goes to the nuclei-not just to the cells but to the nuclei," contends De Stasio, who developed and oversees SPHINX Electron Microscopethe X-ray PhotoElectron Emission spectroMicroscopy (X-PEEM) program at UW Madison's Synchrotron Radiation Center [http://www.src.wisc.edu], where she also serves as interim scientific director.

    De Stasio, like all scientists involved in research programs that may someday lead to cures, is deliberate about the process she and her colleagues are following in the study of gadolinium, noting that the next steps will lead toward animal and possibly human clinical trials.

    "Now that we've proven that it works on cells, let's see if it works on animals. If we do see that we can cure animals from their cancers, then it's worth investigating the molecular biology of this drug and seeing what the uptake mechanism is. But first you want to know that it works and that it really has potential for saving lives. And then you want to put a lot of money into it and a lot of effort and time," she notes.

    Because of the current death sentence status of those who are diagnosed with GBM however, De Stasio knows that this alternative is desperately needed as an alternative to invasive therapies that not only do not offer much promise for a longer life, but are also disruptive to one's quality of life in her or his final days.

    So, how long will this all take before it is a viable option for people with glioblastoma? This is the question she is often asked, says De Stasio. It will be a year before it is known whether or not the treatment works on rats, another five years to know whether it works for patients and perhaps ten before the treatment is available in every hospital-keeping in mind that right now a person would have to go to a synchrotron facility for treatment and that what will be needed, eventually, are miniature synchrotron light sources, similar in size and cost to an MRI machine. But while the time frame seems long and tedious, De Stasio is committed to the mind boggling hours she puts in for the sake of this research.

    "It's the most lethal cancer there is," De Stasio laments. "But fighting it is the type of work that makes you feel good about being a scientist. If you can really contribute to humanity and do something that's useful for people, for sick people, it's really incredibly gratifying."

     

    Motexafin-Gadolinium Taken Up in Vitro by >90% of Glioblastoma Cell Nuclei. Gelsomina De Stasio, Deepika Rajesh, Judith M. Ford, Matthew J. Daniels, Robert J. Erhardt, Bradley H. Frazier, Tolek Tyliszczak, Mary K. Gilles, Robert L. Conhaim, Steven P. Howard, John F. Fowler, Francois Estève, and Minesh P. Mehta.

    Corresponding author:

    Gelsomina "pupa" De Stasio, University of Wisconsin - Madison
    (email: pupa@src.wisc.edu; Ph: 608-877-2000; Fax: 608-877-2001; Web site: http://users.src.wisc.edu/spectromicroscopy/default.htm).