RESPONSE OF RAT SKIN TO BORON NEUTRON-CAPTURE THERAPY WITH P-BORONOPHENYLALANINE OR BOROCAPTATE SODIUM

The effects of boron neutron capture irradiation employing either BPA or BSH as neutron capture agents has been assessed using the dorsal sk in of Fischer 344 rats. Pharmacokinetic studies, using prompt gamma sp ectrometry, revealed comparable levels of boron-10 (B-10) in blood and skin after the intravenous infusion of BSH (100 mg/kg body wt.). The B-10 content of blood (12.0 +/- 0.5 mu g/g) was slightly hig her than that of skin (10.0 +/- 0.5 mu g/g) after oral dosing with BPA. Biphasi c skin reactions were observed after irradiation with the thermal neut ron beam alone or in combination with BPA or BSH. The time of onset of the first phase of the skin reaction, moist desquamation, was similar to 2 weeks. The time at which the second-wave skin reaction, dermal n ecrosis, became evident was dose-related and occurred after a latent i nterval of greater than or equal to 24 weeks, well after the acute epi thelial reaction had healed. The incidence of both phases of skin dama ge was also dose-related. The radiation doses required to produce skin damage in 50% of skin sites (ED(50) values) were calculated from dose -effect curves and these values were used to determine relative biolog ical effectiveness (RBE) and compound biological effectiveness (CBE) f actors for both moist desquamation and dermal necrosis. It was conclud ed on the basis of these calculations that the microdistribution of th e two neutron capture agents had a critical bearing on the overall bio logical effect after thermal neutron activation. BSH, which was possib ly excluded from the cytoplasm of epidermal cells, had a low CBE facto r value (0.56 +/- 0.06) while BPA, which may be selectively accumulate d in epidermal cells had a very high CBE factor (3.74 +/- 0.7). For th e dermal reaction, where vascular endothelial cells represent the like ly target cell population, the CBE factor values were comparable, at 0 .73 +/- 0.42 and 0.86 +/- 0.08 for BPA ad BSH, respectively.