BORON NEUTRON-CAPTURE IRRADIATION OF THE RAT SPINAL-CORD - EFFECTS OFVARIABLE DOSES OF BOROCAPTATE SODIUM

The Fischer 344 rat spinal cord model has been used to evaluate the re sponse of the central nervous system to boron neutron capture irradiat ion with variable doses of the neutron capture agent, borocaptate sodi um (BSH). Three doses of BSH, 190, 140 and 80 mg/kg body weight, admin istered by i.p. injection, were used to establish the time course of B -10 accumulation in and removal from the blood. After administration o f the two lower doses of BSH, blood B-10 levels peaked at 0.5 h after injection, with no significant (P > 0.1) change at 1 h after injection . Beyond this time point, levels of B-10 in the blood began to decreas e after a dose of 80 mg/kg BSH, but remained constant until 3 h after administration after the two higher doses of BSH. Myelopathy developed after latent intervals of 20.4 +/- 0.1, 20.8 +/- 1.4, 15.0 +/- 0.8, 1 5.4 +/- 0.4 and 15.6 +/- 0.4 weeks, following irradiation with thermal neutrons in combination with BSH at doses of 20, 40, 80, 140 and 190 mg/kg body weight, respectively. The radiation-induced lesion in the s pinal cord was white matter necrosis. ED(50) values for myelopathy wer e calculated from probit-fitted dose-effect curves. Expressed as total physical absorbed doses, these values were 20.7 +/- 1.9, 24.9 +/- 1.2 , 27.2 +/- 0.9, 28.4 +/- 0.6 and 32.4 +/- 1.9 Gy after irradiation wit h thermal neutrons in the presence of 20, 40, 80, 140 and 190 mg/kg bo dy weight of BSH, respectively. The compound biological effectiveness (CBE) factor values, estimated from this data, were in the range 0.49- 0.55. There was no significant (P > 0.1) variation in the CBE factor f or BSH as a function of increasing B-10 concentration in the blood. It was concluded that there was no significant synergistic interaction b etween the low and high linear energy transfer (LET) components of the boron neutron capture (BNC) radiation field.