Boron Neutron Capture Therapy (BNCT) is an advanced dual step approach to treating cancer in humans. There are two components to BNCT. First, a boron-containing compound is intravenously injected into the patient. This boron containing compound accumulates at higher concentrations in the tumor than in nearby normal tissues. Next a beam of low-energy neutrons is directed at the boron-containing tumor. The boron atoms capture the neutrons and split into two highly charged particles (alpha particle and lithium ion) that have very short path lengths (approximately one cell diameter). These charged particles release sufficient energy locally to kill any tumor cells containing high concentrations of boron without appreciably harming non-tumor cells that contain low concentrations of boron (selective cell surgery by radioactivity). The success of this approach to tumor treatment is heavily dependent on the availability of boron containing molecules that are non-toxic and that show high selective localization in the tumor to be treated.
DOE is supporting a nation-wide research program for developing BNCT for clinical use. Research funding has been committed to: (1) development of suitable neutron beams using either reactors or accelerators as neutron sources; (2) development and evaluation of boron-carrying compounds such as amino acids, porphyrins, nucleosides, amines, lipoproteins, and liposomes; (3) preclinical studies dealing with pharmacokinetics and biodistribution of boron-carrying compounds, radiation dosimetry and radiation biology in cell systems, and BNCT experiments in small and large animal models; (4) Phase I clinical trials to assess boron-compound biodistribution, to plan treatment software, and to define the limits of safety for BNCT with gradual escalation of the doses for both the boron-carrying compound and the neutron dose, in compliance with regulatory obligations.
The Phase I clinical research trials are limited to evaluation of BNCT in patients with (1) malignant primary brain tumors (glioblastoma multiforme) or (2) malignant melanoma metastases to the brain or (3) malignant skin tumors (melanoma) located on the extremities. The trials involving patients with glioblastoma multiforme are conducted at both the Brookhaven National Laboratory (BNL) in collaboration with the Beth Israel Medical Center (BIMC) in New York, NY, and at the Harvard-MIT program involving the Massachusetts Institute of Technology in collaboration with the Beth Israel Deaconess Medical Center in Boston. The melanoma treatment trials are conducted only at the Harvard-MIT program.
The two BNCT Phase I clinical trials are nearing completion. To date, the results suggest BNCT therapy of brain tumors is not associated with substantially greater toxicity that that encountered after conventional post-surgical radiation therapy. Moreover, patients have welcomed the relatively short treatment period required by the BNCT approach. The current clinical trials are still engaged in defining the optimum mixture of treatment components, i.e. the best combination of boron compound dose and neutron flux.
The clinical Phase I trials in patients with skin melanomas have shown some early success in temporarily eradicating several melanomas without significant local or systemic toxicity to healthy tissue from the boron compound and neutron irradiation.
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National Laboratories:
Brookhaven National Laboratory;
Idaho National Engineering Laboratory.
Academic Institutions: University of California, Los Angeles; University of California, San Francisco; Cornell University; Harvard University, New England Deaconess-Beth-Israel Medical Center; Massachusetts Institute of Technology; Ohio State University; University of Tennessee, Knoxville; Washington State University. |
| The final report on the DOE workshop, The Clinical State of Boron Neutron Capture Therapy 1997, that was held November 3-5, 1997, in Charlotte, North Carolina Is being published by the Department of Energy. A electronic copy of the report can be obtained by downloading the following Adobe PDF files or a hard copy of the report can be obtained by contacting: Sharon Betson, sharon.betson@oer.doe.gov |
Program Contact:
Peter Kirchner, M.D.
e-mail: Peter.kirchner@science.doe.gov