Boron neutron capture therapy of a murine melanoma with p-boronophenylalanine: dose-response analysis using a morbidity index.

Boron-10 concentrations of 20 or 40 micrograms/g were attained in mouse B16 melanomas following one or two intragastric doses of p-boronophenylalanine (750 mg/kg body weight per dose), respectively. Tumor-to-normal-tissue (blood, muscle) boron concentration ratios were 4:1-6:1. The efficacy of boron neutron capture irradiation was monitored using the Wilcoxon two-sample test in conjunction with a system of ranking outcomes of different therapies that compared living mice and mice sacrificed because of excessive tumor growth concomitantly. Median survivals were extended progressively as radiation doses were increased up to 38.7 gray-equivalent (gray X relative biological effectiveness), with one of five and one of six tumors cured in each of the two highest dose groups, respectively. When comparable tumor inhibitory doses of 250-kVp X rays were used to treat these tumors, instead of the transient erythema and edema that resulted from boron neutron capture therapy, there resulted irreversible muscle necrosis in the irradiated zone and atrophy of the foot distal to the irradiated zone. The improvement in treatment outcome with boron neutron capture therapy is attributable to unprecedented tumor-to-normal-tissue radiation dose ratios of approximately 2.8 to 3.6.