Boron neutron capture therapy of intracerebral melanoma using boronophenylalanine as a capture agent

A rat brain tumor model has been developed utilizing nude rats and the human melanoma cell line MRA 27. For pharmacokinetic and tissue distribution studies, 2 10(5) MRA 27 cells were implanted intracerebrally (i.c.), and 30 days later, 120 mg of 10B-enriched L-boronophenylalanine were injected i.p. into nude rats. 10B concentrations in the tumor, blood, and normal brain were 23.7, 9.4, and 8.4 micrograms/g, respectively, 6 h following administration. For therapy experiments, tumor bearing rats were irradiated at the Brookhaven Medical Research Reactor 30 days following implantation. The median survival time was 44 days for untreated rats, 76 days for those receiving a physical dose of 2.7 Gy, and 93 days for those receiving 3.6 Gy. Animals receiving both 10B-L-boronophenylalanine and physical doses of 1.8, 2.7, or 3.6 Gy (total tumor physical doses of 5.0, 7.5, or 10.1 Gy) had median survival times of 170, 182, and 262 days, respectively. Forty % of rats that received the highest tumor dose (10.1 Gy) survived > 300 days. In a replicate experiment 21% of animals that had received L-boronophenylalanine and irradiation (total tumor physical dose of 10.1 Gy) were alive 220 days after therapy. In a parallel study, animals that were irradiated with gamma photons from a 137Cs source with 12 Gy or 2.0 Gy 9 delivered to the head had median survival times of 86 and 79 days, respectively, compared to 47 days for untreated animals. Our results indicate that boron neutron capture therapy is effective against i.c. melanoma in a rodent model and suggest that large animal studies are warranted to further assess its efficacy.