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Boron Neutron Capture Therapy for Murine Malignant Gliomas¹

Departments of Neurosurgery [S. C. S., G. C., S. E. K.], Radiation Oncology [G. R. S., D. E. W., R. G. Z., M. A. J., H. M-J.], and Neuropathology [L. S. A.], Tufts University School of Medicine and the New England Medical Center, Boston, Massachusetts 02111, and Nuclear Reactor Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 [O. K. H.]

Boron neutron capture therapy (BNCT) involves administration of a boron compound followed by neutron irradiation of the target organ. The boron atom captures a neutron, which results in the release of densely ionizing helium and lithium ions that are highly damaging and usually lethal to cells within their combined track length of approximately 12 µm. Prior to Phase I clinical trials for patients with malignant gliomas, mice with glioma 261 intracerebral tumors were fed D,L-3-(p-boronophenyl)alanine and irradiated with total tumor doses of 1000–5000 RBE-cGy of single fraction thermal neutrons to determine the maximum tolerated dose and effect on survival. These mice were compared to mice that received D,L-3-(p-boronophenyl)alanine alone, neutron irradiation alone, photon irradiation alone, or no treatment. Additional normal mice received escalating doses of neutron irradiation to determine its toxicity to normal brain.

BNCT caused a dose-dependent, statistically significant prolongation in survival at 1000–5000 RBE-cGy. At 3000 RBE-cGy, median survival rates of the BNCT and untreated control groups were 68 and 22 days, respectively, with a long-term survival rate of 33%. At 4000 RBE-cGy, median survival was 72 and 21 days, respectively, with a long-term survival rate of 43%. At lower radiation doses, the extended survival was comparable between the BNCT and photon-irradiated mice; however, at 3000 and 4000 RBE-cGy the median survival of BNCT-treated mice was significantly greater than photon-irradiated mice. The maximum tolerated single fraction dose to normal brain was approximately 2000 RBE-cGy.

¹ Work supported by Department of Energy Grant FG02 ER6060 and Biomedical Research Support Grant S07-RR05598 from the New England Medical Center.

² To whom requests for reprints should be addressed, at Department of Neurosurgery, New England Medical Center, Box 178, 750 Washington Street, Boston, MA 02111.

Received 1/24/92. Accepted 6/24/92.

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