Boron neutron capture therapy: long-term effects on the skin and spinal cord of the rat.
Our studies of the pharmacokinetics of boron focused on the variations in the concentration in blood of Sprague-Dawley rats with time after the administration of single intravenous doses of 50-200 mg/kg of 10B-enriched sodium mercaptoundecahydro-closo-dodecaborate (BSH). After the lowest dose of BSH there was a progressive decline in the boron content of the blood, with a biological half-life (t1/2) of approximately 4.5 h. Higher doses of BSH resulted in slower boron clearance rates. A dose of 100 mg/kg of BSH was the maximum safely tolerated by the rats. The boron content of the skin at this dose of BSH was a factor of 0.6 lower than that in the blood. To determine the dose-related changes in the response of the central nervous system to BNCT-type radiation exposures, a well-established and clinically relevant model, the rat spinal cord, was used. The spinal cords (20 mm field length) of rats, infused with 100 mg/kg of BSH, were irradiated for 3 to 5 h with cold thermal neutrons from the H6 beam on the DIDO reactor (AERE, Harwell). The skin surface neutron flux was 4.8 x 10(8) n/cm2/s. Exposure times of > or = 4 h resulted in vigorous, biphasic skin reactions, indicative of long-term vascular damage in the dermis. Rats were monitored closely for 84 weeks after irradiation. No abnormal neurological responses were observed and there was no histological evidence of lesions in the spinal cord at the end of the study. These findings indicate that the central nervous system has a high tolerance to BNCT-type radiation using BSH as the neutron capture agent.
CRC Normal Tissue Radiobiological Research Group, Research Institute (University of Oxford), Churchill Hospital, United Kingdom.
G M
GM
Morris
G
G
Constantine
G
G
Ross
T K
TK
Yeung
J W
JW
Hopewell
D000818:Animals; D001894:Borohydrides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001895:Boron / Q000032:analysis*; D016754:Boron Neutron Capture Therapy; D004307:Dose-Response Relationship, Radiation; D008297:Male; D011833:Radiation Injuries, Experimental; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D013116:Spinal Cord / Q000378:metabolism / Q000528:radiation effects*; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*
D001894:Borohydrides; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D001895:Boron