Of the approximately 12,000 people who are diagnosed with glioblastoma multiforme annually in the U.S., half will die within a year, and the rest within 3 years.

Currently, the only treatments that stretch survival limits are exceptionally invasive surgeries to remove the tumor and radiation treatment with the maximum tolerated dose - all of which leads to a painfully low quality of life. Because of this, researchers are racing to find better therapies to stop or slow glioblastoma multiforme.

In the journal Clinical Cancer Research, Gelsomina "Pupa" De Stasio, at the University of Wisconsin-Madison, and her colleagues report on research into using a new radiotherapy technique for fighting glioblastoma multiforme with the element gadolinium. The approach might some day lead to less invasive treatment and possibly a cure of this disease.

" 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," says De Stasio. 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 is 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," De Stasio says. "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 adds that, for the treatment to be effective, gadolinium must be absent from normal cells and 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 microscopy techniques at the Synchrotron Radiation Center ( SRC ) in Stoughton.

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

De Stasio developed and oversees the X-ray PhotoElectron Emission spectroMicroscopy ( X-PEEM ) program at UW Madison's SRC.

The technology necessary for eventual treatment would involve miniature synchrotron light sources, which could be similar in size and cost to an MRI machine. De Stasio says the next steps will include animal and possibly human clinical trials.

" 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," she says. "But first, you want to know that it works and that it really has potential for saving lives."

Because of the deadly nature of glioblastoma multiforme, De Stasio says an alternative is desperately needed to current therapies that offer little promise for extending life.
De Stasio says it will be a year before it is known whether the treatment works in animal models, and likely another five to ten years before clinical trials and available treatments would emerge.

Source: University of Wisconsin-Madison, 2006


XagenaMedicine2006