BORON NEUTRON-CAPTURE THERAPY - A GUIDE TO THE UNDERSTANDING OF THE PATHOGENESIS OF LATE RADIATION-DAMAGE TO THE RAT SPINAL-CORD

Purpose: Before the commencement of new boron neutron capture therapy (BNCT) clinical trials in Europe and North America, detailed informati on on normal tissue tolerance is required. In this study, the patholog ic effects of BNCT on the central nervous system (CNS) have been inves tigated using a rat spinal cord model. Methods and Materials: The neut ron capture agent used was B-10 enriched sodium mercaptoundecahydro-cl oso-dodecaborate (BSH), at a dosage of 100 mg/kg body weight. Rats wer e irradiated on the thermal beam at the Brookhaven Medical Research Re actor. The large spine of vertebra T-2 was used as the lower marker of the irradiation field. Rats were irradiated with thermal neutrons alo ne to a maximum physical absorbed dose of 11.4 Gy, or with thermal neu trons in combination with BSH, to maximum absorbed physical doses of 5 .7 Gy to the CNS parenchyma and 33.7 Gy to the blood in the vasculatur e of the spinal cord. An additional group of rats was irradiated with 250 kVp X rays to a single dose of 35 Gy. Spinal cord pathology was ex amined between 5 and 12 months after irradiation.Results: The physical dose of radiation delivered to the CNS parenchyma, using thermal neut ron irradiation in the presence of BSH, was a factor of two to three l ower than that delivered to the vascular endothelium, and could not ac count for the level of damage observed in the parenchyma. Conclusion: The histopathological observations of the present study support the hy pothesis that the blood vessels, and the endothelial cells in particul ar, are the critical target population responsible for the lesions see n in the spinal cord after BNCT type irradiation and by inference, aft er more conventional irradiation modalities such as photons or fast ne utrons.