A nude rat model for neutron capture therapy of human intracerebral melanoma

Abstract

Purpose : The present study was carried out to determine the efficacy of Boron Neutron Capture Therapy (BNCT) for intracerebral melanoma using nude rats, the human melanoma cell line MRA 27, and boronophenylalanine as the capture agent. Methods and Materials : Pharmacokinetic and tissue distribution studies: MRA 27 cells (2 X 10 5) were implanted intracerebrally, and 30 days later, 120 mg of 10B-L-BPA were injected intraperitoneally into nude rats. Therapy experiments: Thirty days following implantation, tumor bearing rats were irradiated at the Brookhaven Medical Research Reactor. Results : Pharmacokinetic experiments: Six hours following administration of BPA, tumor, blood, and normal brain boron-10 levels were 23.7, 9.4, and 8.4 μ/g respectively. Therapy experiments: Median survival time of untreated rats was 44 days compared to 76 days and 93 days for those receiving physical doses of 2.73 Gy and 3.64 Gy, respectively. Rats that had received both 10B-BPA and physical doses of 1.82, 2.73, or 3.64 Gy had median survival times of 170, 182, and 262 days, respectively. Forty percent of rats that had received the highest tumor dose (10.1 Gy) survived for > 300 days and in a replicate experiment 21% of the rats were longterm survivors (> 220 days). Animals that received 12 Gy in a single dose or 18 Gy fractionated (2 Gy X 9) of gamma photons from a 137Cs source had median survival times of 86 and 79 days, respectively, compared to 47 days for untreated animals. Histopathologic examination of the brains of longterm surviving rats, euthanized at 8 or 16 months following BNCT, showed no residual tumor, but dense accumulations of melanin laden macrophages and minimal gliosis were observed. Conclusion : Significant prolongations in median survival time were noted in nude rats with intracerebral human melanoma that had received BNCT thereby suggesting therapeutic efficacy. Large animal studies should be carried out to further assess BNCT of intracerebral melanoma before any human trials are contemplated.