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Targeting Tumors

“Boron Neutron Capture Therapy” (BNCT) is an experimental form of radiation therapy that could more effectively target lethal cancers.

Advanced treatment planning software is a significant outcome of ongoing INEEL research.

Although “glioblastoma multiforme” doesn't sound nearly as scary as “incurable brain tumor,” that's exactly what it is. The brain's support cells start growing out of control and strangle the organ with tentacles of malignant tissue. This type of cancer strikes more than 10,000 Americans each year and kills half of them in 12 months. Within two years, ninety percent of those stricken are dead.

Sadly, treatment for this condition has improved little in the last 25 years. Glioblastoma multiforme — the most malignant form of brain tumor-infiltrates the brain so aggressively that surgeons are rarely able to remove all the cancerous tissue. And these types of tumors are resistant to standard radiation treatment and chemotherapy.

But researchers around the world have been studying the innovative treatment called BNCT that might offer hope to patients and their doctors. Nuclear science from the Idaho National Engineering and Environmental Laboratory is having an international impact on this research. For three years, scientists at the U.S. Department of Energy's INEEL have been collaborating with a group in Argentina, which recently began human trials of the technique. The fruits of this ongoing collaboration-established under a formal bilateral treaty supporting peaceful uses of nuclear science-may significantly improve treatment outcome, say the scientists.

BNCT - A Targeted Tumor Attack

The BNCT method involves delivery of concentrated doses of radiation directly to tumors while sparing non-cancerous tissues. The technique requires targeting malignant tissue with a carrier of elemental boron-10, then exposing the area to a beam of neutrons. The result is the release of radiation wherever neutrons encounter boron.

“When a neutron collides with a boron atom, an alpha particle and a lithium ion are produced,” said David Nigg, the INEEL physicist overseeing the BNCT research. "These highly energetic charged particles won't travel farther than the width of a cell, ideally leading to selective destruction of the tumor and sparing the neighboring normal tissue."

So, only cells harboring boron receive high doses of radiation. Treatment success depends on loading the tumor cells with boron while sparing surrounding healthy tissue, researchers explain. To achieve this, scientists attach boron-10 to a “delivery agent” that has an affinity for tumor cells. Right before treatment, patients ingest the agent either orally or intravenously and boron accumulates in the tumor.

The Food and Drug Administration has approved only three such “boron delivery agents” for human use, Nigg said. One of these agents, called GB-10, had been difficult to obtain and thus impractical for extensive research projects.

INEEL Researchers Offer Contributions

Scientists obtain GB-10 from a precursor that is difficult to synthesize, said Nigg. But several years ago, INEEL scientists developed a better way to make the precursor, he said. Working through Neutron Therapies, LLC via a Cooperative Research and Development Agreement, INEEL researchers have facilitated the synthesis and testing of significant amounts of GB-10. Their collaborators at Washington State University are planning large animal studies to assess the agent's ultimate suitability for human trials.

INEEL physicist Chuck Wemple demonstrates dosimetry software.

“Now we have enough of it for practical use," said Nigg. "We are the only labs right now using this particular agent.”

Calculating the dose of delivered radiation is also critical-to both treatment planning and basic research, Nigg said. This calculation requires a measurement of the boron content in the tumor and normal tissue as well as a patient-specific model of the complex geometry of the brain.

INEEL scientists have developed unique software that uses a precise computational model to calculate the doses of delivered radiation, Nigg said. The software-called Simulation Environment for Radiotherapy Applications or SERA-is currently used in connection with BNCT clinical trials in Finland and in Sweden, and it is being phased into clinical use for trials in the Netherlands. The South American collaborators also rely on the SERA software for some aspects of their studies.

Bilateral Treaty Nurtures Collaboration

For three years, INEEL researchers have collaborated with scientists at the National Atomic Energy Commission of Argentina (CNEA) under the terms of the “Technical Exchange and Cooperation in the Area of Peaceful Uses of Nuclear Energy” that was signed in October 1997. This “Sister Laboratory Arrangement” involves several U.S. research institutions. The INEEL studies are supported by the National Nuclear Security Administration. Additional support came from the DOE Office of Science in 2003 and 2004.

The INEEL is the only national laboratory participating in the BNCT arm of the program, Nigg said. The arrangement was highlighted at a Joint Standing Committee meeting between the state departments of the U.S. and Argentina in August 2003.

“Our collaboration was one of the most prominently featured,” Nigg said. The researchers also hope to get recognition for this collaboration at the 11th International Congress for Neutron Capture Therapy in September 2004 and at the DOE-sponsored America's Nuclear Energy Symposium-a Joint North and South America technical meeting on peaceful uses of nuclear technology-in October 2004.

A Fruitful Arrangement

In October 2003, the Argentinean researchers began human BNCT trials, Nigg said. In collaboration with INEEL researchers, the Argentinean scientists are investigating the new boron delivery agent in animal trials that could lead to future use of this particular agent in their human trials as well.

INEEL physicist David Nigg, fourth from right, and INEEL chemist Bill Bauer, far right, with CNEA collaborators in their Argentine research center.

So far, the combined effort between INEEL and CNEA has resulted in three refereed publications and two current submittals, Nigg said. Overall, the DOE-CNEA Sister Laboratory Program has yielded 14 refereed publications, seven presentations at international meetings, and four presentations at Argentine national congresses.

The professional exchange program also provides opportunities for close collaborative relationships between members of the two research groups. For example, Argentinean researcher Maria Julia Roberti visited the INEEL in March 2003 and was able to work closely with the INEEL Analytical Chemistry Group. Conversely, Nigg and INEEL scientists William Bauer and John Hartwell traveled to the South American lab in May 2003 to conduct joint experimental activities in both neutron physics and chemistry.

“This has been an enormously valuable collaboration for both sides,” Nigg said.