Agent shows promise for treating brain tumors

A chemical agent long used by physicians to get detailed pictures of cancer tumors may also have therapeutic value for a class of deadly brain tumors, according to a new study.

The study, published May 15 in the journal Cancer Research, demonstrates that gadolinium compounds, contrasting agents used in Magnetic Resonance Imaging (MRI) to illuminate tumors, can be absorbed by cancer cells where, in combination with thermal neutron treatment, they can destroy the DNA that cancer cells depend on to live and reproduce.

“It’s like a small atomic bomb,” says Gelsomina De Stasio, a UW–Madison professor of physics and the lead author of the study. “There is going to be a very strong and very destructive reaction where the gadolinium is situated” when it is exposed to low-energy neutrons while sparing nearby healthy tissue that does not contain gadolinium.

Gadolinium has been used for more than 15 years in MRI as a contrast agent to light up the tumor cells. But it has long been assumed to have no therapeutic value because it was thought that it could not be absorbed by cancer cells. The new study shows, however, that gadolinium is indeed absorbed by cancer cells where it migrates to the nucleus and can be triggered by thermal neutron radiation to destroy the cancer cell DNA.

“Everybody thought gadolinium therapy was not possible,” says De Stasio. “It was assumed that gadolinium compounds remained extracellular

in tumor tissue and could not reach the cell nucleus. We show that that is not the case.”

The results of the study, conducted at UW–Madison’s Synchrotron Radiation Center, in collaboration with researchers in Italy, Switzerland and Montana, suggest that new gadolinium-compound therapies could be developed to treat glioblastoma, a brain cancer that kills an estimated 12,000 people every year in the United States alone. “It’s a very nasty tumor and usually kills patients within six months of diagnosis,” De Stasio says.

In the past, similar therapies employing boron compounds have been attempted, and are used widely in places such as Japan. But gadolinium compounds seem to be much more specific for tumor cells and, once absorbed into the cell nucleus, provide a much bigger target for the neutrons that provoke the DNA-destroying reaction.

The study published in Cancer Research was conducted in cultured tumor cells. Therapies involving gadolinium compound isotopes have not yet been tried in humans, but studies of how well the compounds are absorbed by tumor cells in patients are now underway. If successful, the new studies could lead to a non-invasive and non-toxic treatment for glioblastoma patients.