BORON NEUTRON-CAPTURE THERAPY OF BRAIN-TUMORS - ENHANCED SURVIVAL FOLLOWING INTRACAROTID INJECTION OF EITHER SODIUM BOROCAPTATE OR BORONOPHENYLALANINE WITH OR WITHOUT BLOOD-BRAIN-BARRIER DISRUPTION

The purpose of the present study was to determine whether the efficacy of boron neutron capture therapy could be enhanced by means of intrac arotid (i.c.) injection of sodium borocaptate (BSH) or boronophenylala nine (BPA) with or without blood-brain barrier disruption (BBB-D). For biodistribution studies, F98 glioma-bearing rats were injected i.v. o r i.c. with either BSH (30 mg of boron/kg of body weight) or BPA (24 m g of boron/kg of body weight) with or without mannitol-induced, hypero smotic BBB-D and killed 2.5 h later, The highest tumor boron concentra tions for BSH and BPA were attained following i.c. injection with BBB- D (48.6 and 94.0 mu g/g, respectively) compared to i.c. (30.8 and 42.7 mu g/g) and i.v. injection (12.9 and 20.8 mu g). Using the same doses of BSH and BPA, therapy experiments were initiated 14 days after intr acerebral implantation of F98 glioma cells. Animals were irradiated 2. 5 h after i.v. or i.c. administration of the capture agent with or wit hout BBB-D using a collimated beam of thermal neutrons at the Brookhav en Medical Research Reactor. The median survival times of rats given B SH or BPA i.c. were 52 and 69 days, respectively, for rats with BBB-D; 39 and 48 days for rats without BBB-D; 33 and 37 days for i.v. inject ed rats; 29 days for irradiated controls; and 24 days for untreated co ntrols. i.e injection of either BSH or BPA resulted in highly signific ant enhancement (P = 0.01 and P = 0.0002, respectively) of survival ti mes compared to i.v. injection, and this was further augmented by BBB- D (P = 0.02 and P = 0.04, respectively) compared to i.e injection. Nor mal brain tissue tolerance studies were carried out with non-tumor-bea ring rats, which were treated in the same way as tumor-bearing animals , One year after irradiation, the brains of these animals showed only minimal radiation-induced changes in the choroid plexus, but no differ ences were discernible between irradiated controls and those that had BBB-D followed by i.c. injection of either BSH or BPA. Our data clearl y show that the route of administration, as well as BBB-D, can enhance the uptake of BSH and BPA, and, subsequently, the efficacy of boron n eutron capture therapy.