BORON NEUTRON-CAPTURE THERAPY OF A RAT GLIOMA

The purpose of the present study was to utilize a well-established rat glioma to evaluate boron neutron capture therapy for the treatment of malignant brain tumors. Boron-10 (10B) is a stable isotope which, when irradiated with thermal neutrons, produces a capture reaction yielding high linear energy transfer particles (10B + 1n(th) → [11B] → 4He(α) + 7Li + 2.79 MeV). The F98 tumor is an anaplastic glioma of CD Fischer rat origin with an aggressive biological behavior similar to that of human glioblastoma multiforme. F98 cells were implanted intracerebrally into the caudate nuclei of Fischer rats. Seven to 12 days later the boron-10-enriched polyhedral borane, Na2B12H11SH, was administered intravenously at a dose of 50 mg/kg body weight at varying time intervals ranging from 3 to 23.5 hours before neutron irradiation. Pharmacokinetic studies revealed blood 10B values ranging from 0.33 to 10.5 μg/ml depending upon the time after administration, a T( 1/2 ) of 6.2 hours, normal brain 10B concentrations of 0.5 μg/g, and tumor values ranging from 1.1 to 12.8 μg/g. No therapeutic gain was seen if the capture agent was given at 3 or 6 hours before irradiation with 4 x 1012 n/cm2 (10 MW-min; 429 cGy). A 13.5-hour preirradiation interval resulted in a mean survival of 37.8 days (P<0.01), compared to 30.5 days (P<0.03) for irradiated controls and 22.1 days for untreated animals. Rats given the capture agent 16 hours before irradiation had a mean survival time of 41 days (P<0.005) compared to 27.7 days for unirradiated and 35.8 days (P<0.01) for irradiated control rats. In vitro studies with F98 cells demonstrated a 3 to 4 log reduction in the surviving fraction using Na2B12H11SH at concentrations of 50 or 100 μg/ml and a fluence of 1013 n/cm2. The in vivo data show enhanced survival in brain tumor-bearing rats that have been treated by boron neutron capture therapy and the in vitro data suggest that even better results might be achievable if tumor concentrations of 10B can be increased.