title: Boron neutron capture irradiation of the rat spinal cord: effects of variable doses of borocaptate sodium.
abstract: The Fischer 344 rat spinal cord model has been used to evaluate the response of the central nervous system to boron neutron capture irradiation with variable doses of the neutron capture agent, borocaptate sodium (BSH). Three doses of BSH, 190, 140 and 80 mg/kg body weight, administered by i.p. injection, were used to establish the time course of 10B accumulation in and removal from the blood. After administration of the two lower doses of BSH, blood 10B 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 10B in the blood began to decrease 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, 15.4 +/- 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 spinal cord was white matter necrosis. ED50 values for myelopathy were 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 with thermal neutrons in the presence of 20, 40, 80, 140 and 190 mg/kg body 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 for BSH as a function of increasing 10B concentration in the blood. It was concluded that there was no significant synergistic interaction between the low and high linear energy transfer (LET) components of the boron neutron capture (BNC) radiation field.
authors.affiliation: CRC Normal Tissue Radiobiological Research Group, University of Oxford, Churchill Hospital, UK.
authors.forename: G M
authors.initials: GM
authors.lastname: Morris
authors.forename: J A
authors.initials: JA
authors.lastname: Coderre
authors.forename: J W
authors.initials: JW
authors.lastname: Hopewell
authors.forename: P L
authors.initials: PL
authors.lastname: Micca
authors.forename: C
authors.initials: C
authors.lastname: Fisher
mesh_terms: D000818:Animals; D001894:Borohydrides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects; D002490:Central Nervous System / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000473:pathology / Q000528:radiation effects*; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D001894:Borohydrides; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate