The phrase "Boron Neutron Capture Therapy (BNCT)" designates an experimental approach to cancer treatment which is based on a dual step technique utilizing two linked treatment components. First, a boron-containing compound is intravenously injected into the test animal or 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 approximating one cell diameter. These charged particles release sufficient energy locally to kill any tumor cells containing high concentrations of boron without appreciably harming cells that contain low concentrations of boron (selective cell surgery by radiation targeting). 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 in-vivo localization in the tumor to be treated. Boron compounds currently available for human studies have only moderate selectivity for tumor cells.

DOE has supported a nation-wide research program for developing BNCT for clinical use. DOE research funding has been committed to: (1) development of suitable neutron beams, using either reactors or accelerators as neutron sources; (2) development and evaluation for clinical suitability of various boron-carrying compounds such as boronated amino acids, porphyrins, nucleosides, amines, lipoproteins, and liposomes; (3) pre-clinical studies dealing with pharmacokinetics and biodistribution of boron-carrying compounds in animals and humans, radiation dosimetry estimations, radiation biology experiments 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 assess toxicity and to define the limits of safety for BNCT, with gradual escalation of the doses for both the boron-carrying compound (boronated phenyalanine – BPA) and the neutron dose.

The Phase I clinical research trials were limited to the evaluation of safety and toxicity of BNCT in patients with (1) malignant primary brain tumors (glioblastoma multiforme) or (2) malignant melanoma metastases to the brain or (3) malignant melanoma located on the extremities. The trials involving patients with glioblastoma multiforme were conducted at both the Brookhaven National Laboratory (BNL) in collaboration with the Beth Israel Medical Center in New York, NY, and at the Harvard-MIT Program involving a close collaboration between the Massachusetts Institute Of Technology and the Beth Israel Deaconess Medical Center in Boston. The safety trials involving melanoma patients were conducted only at the Harvard-MIT Program.

The Phase I dose-escalation trials at both BNL and Harvard-MIT were able to define approximate upper limits of safety for normal tissues for their respective beams, and both programs are now closed to new patients. Intensive efforts are directed at completing the collection of follow-up data for scientific publications.

The results of the clinical trial with BPA-based BNCT suggest that the delivery of the boron compound to glioblastomas may not be sufficiently selective. It is also clear that better biodistribution measures for the boron compound are needed to conduct meaningful clinical trials. DOE's Biological & Environmental Research Advisory Committee (BERAC) commissioned an external review of DOE's BNCT program. The ensuing November 1999 subcommittee report to BERAC did not endorse continuation of DOE support for these clinical trials and recommended that support for any future clinical trials be obtained from the National Cancer Institute or other agencies. Continued funding of basic BNCT research was to be based on DOE's programmatic interests. This recommendation has been accepted by BERAC and by the Office of Biological and Environmental Research (BER).

Currently, BER continues to provide limited support to basic research directed at the development and evaluation of new, more effective BNCT compounds that could be used alone, or in combination with BPA. Modest support is continuing also to optimize the use of tissue cultures and animal tumor models for testing promising new boron compounds. DOE support of neutron beam development for clinical trials will be limited, pending the refinement of more successful boron compounds.

Revised, April 10, 2000

Program Contractors

BNCT Workshop Report

Program Contact:

Peter Kirchner, M.D.
e-mail: Peter.kirchner@science.doe.gov