July 3, 2001
Brookhaven Lab and Psimei Pharmaceuticals Ltd. Develop Boron Compounds For Potential Cancer Treatments
Upton, NY - The Department of Energy's Brookhaven National Laboratory and Psimei Pharmaceuticals Limited have signed a Cooperative Research and Development Agreement (CRADA) to develop Brookhaven-invented boron compounds for use in an experimental radiation therapy for cancer, as well as in other cancer treatments.
Psimei, a recently launched biotechnology company in Middlesex, England, has acquired the license to commercialize the new boron compounds from Brookhaven Science Associates (BSA), the organization that manages Brookhaven for the U.S. Department of Energy. BSA holds U.S. patents and U.S. patent applications covering these compounds and has filed international patent applications, which are pending.
Brookhaven researchers recently performed clinical trials to determine the safety and toxicity limits of an experimental therapy known as boron neutron capture therapy (BNCT) when used with a boronated amino acid called BPA in patients with an incurable brain cancer known as glioblastoma multiforme. In these trials, BNCT was no more effective than conventional therapies in slowing the recurrence of brain tumors.
Compared to BPA, the new boron compounds are expected to deliver higher concentrations of boron to certain tumors than to normal surrounding tissues within the neutron-irradiated regions, which may make the new compounds more effective for BNCT. If pre-clinical studies under the CRADA agreement and subsequent clinical trials find the new compounds to be safe and effective, they may well be used in BNCT for the treatment of head and neck tumors and/or brain tumors. Also, Psimei is involved in the development of a mobile neutron source so that BNCT will be available at hospitals as needed.
In addition to use in BNCT, the new boron compounds may be useful for improving the effectiveness of conventional x-ray therapy, which kills tumors with x-rays; and for photodynamic therapy, in which lasers and photosensitizers destroy tumors. The new boron compounds concentrate preferentially in tumors and destroy cancerous cells when they react with neutrons in BNCT. Researchers expect the same effect in these other therapies, in which photons interact with the boron compounds.
"The most promising new porphyrin contains both boron and copper," said Michiko Miura, Brookhaven's principal investigator in the CRADA. "So far, it looks very effective in destroying tumor tissue, while minimally affecting normal tissue."
In an article to be published in the July 5, 2001 edition of the Journal of Neuro-Oncology, Miura and others report that in initial studies of tumors in mice and rats, the new copper-containing compound delivered up to 250 parts per million of boron to certain tumors, while boron compounds used in BNCT trials to treat brain tumors had only delivered an estimated 30 parts per million boron to the tumor. Also, the tumor:blood boron concentration ratio was greater than 100:1, compared to only 3:1 for previous boron compounds used in BNCT.
In BNCT studies performed at Brookhaven reported in Radiation Research (April 2001), the new compound controlled 70 percent of leg tumors in mice, with little or no normal tissue damage or chemical toxicity to the animals. Under the CRADA, researchers will evaluate the biodistribution and toxicity of the compounds in various types of cancer in mice. If those studies prove favorable, they will perform experiments to determine the therapeutic efficacy of the compound.
Additional compounds will be synthesized that can be imaged using noninvasive diagnostic techniques, such as positron emission tomography and single photon emission computed tomography. Such imaging will allow physicians to view boron concentrations in a patient's tumors and in surrounding normal tissues, which will significantly aid in treatment planning.
The CRADA research is fully funded by Psimei Pharmaceuticals and will take place at Brookhaven and Oxford University. At the same time, the Office of Biological and Environmental Research in the Department of Energy's Office of Science will be providing funding to Brookhaven for complementary research in this field.
The U.S. Department of Energy's Brookhaven National Laboratory
conducts research in the physical, biomedical, and environmental
sciences, as well as in energy technologies. Brookhaven also builds
and operates major facilities available to university, industrial, and
government scientists. The Laboratory is managed by Brookhaven Science
Associates, a limited liability company founded by Stony Brook
University and Battelle, a nonprofit applied science and technology