A review: CNS effects and normal tissue tolerance in dogs

Large animal studies have been utilized to define tolerance of normal brain to irradiation and verify treatment planning programs with two recently installed epithermal neutron beams. The normal brain tolerance studies utilized two biological endpoints, magnetic resonance visible damage only and neurologic signs progressing to death. The studies focused on defining the proton RBE for the contaminant fast neutrons, and from nitrogen capture of thermal neutrons and boron capture reaction biologic effect. The proton RBE was approximately 3.0 to 6.7, depending on whether a dose reduction factor for the low gamma dose rate was employed. The microscopic distribution of the boron compounds, coupled with the extremely short length of the fission fragments from thermal neutron capture by 10B yields an observed biologic effect much less than would be expected from such high LET irradiation. This observed biologic effect, which is a product of the microdistribution of the boron atom and the relative biologic effect of the fission fragments has been termed compound factor. The compound factor was based on the calculated physical dose from the fission fragment in blood based on measured blood 10B concentration. The approximate compound factor for BSH was studied at the two institutions and it ranged from 0.27 to 0.55, depending on the site and the endpoint chosen. The mean compound factor for BPA was only studied at one site and was found to be 1.1 for both endpoints. The increase in the compound factor for BPA is in keeping with previous calculations based on the differences in compound distribution. Results of these studies has helped the initiation of phase I and phase II clinical trials at Brook haven National Laboratory and the planned European clinical trials at Petten, The Netherlands.