Response of the central nervous system to fractionated boron neutron capture irradiation: studies with borocaptate sodium.

The response of the central nervous system (CNS) to fractionated doses of boron neutron capture (BNC) irradiation was assessed using a rat spinal cord model. The thermal neutron beam at the Brookhaven Medical Research Reactor (BMRR) was used for the spinal cord irradiations, with borocaptate sodium (BSH) as the neutron capture agent. Irradiations were given as a single dose or as two or four equal fractions. The ED50 for radiation-induced myeloparesis, as indicated by limb paralysis within 7 months, after a single exposure to thermal neutrons in the presence of BSH (blood boron-10 content approximately 70 micrograms/g) was 27.2 +/- 0.9 Gy. This was expressed as the total physical dose to the blood. Dividing the radiation dose into two consecutive daily fractions or four fractions given over 1 week, resulted in ED50 = 32.0 +/- 1.4 and 31.5 +/- 0.4 Gy respectively. Although there was no significant dose sparing in moving from two to four fractions, there was a dose increment of approximately 17% as compared with single-dose irradiation. The variation in the relative biological effectiveness of the thermal neutron beam, with dose per fraction, was established using data from a previous study with single and fractionated doses of thermal neutrons in the absence of a neutron capture agent. This varied from 1.40 to 3.74 for thermal neutron dose per fraction in the range 13.6-1.5 Gy. Previously published CBE factors for both BSH and BPA have been recalculated in the present report to take into account the change in the RBE of the thermal neutron beam with dose. In all cases the recalculated CBE factors were lower than those obtained previously. Values for this parameter increased with fraction number. In the case of BSH, the CBE factor increased from 0.36 +/- 0.03 after a single-dose to 0.51 +/- 0.06 after four fractions.