A NUDE RAT MODEL FOR NEUTRON-CAPTURE THERAPY OF HUMAN INTRACEREBRAL MELANOMA

Purpose: The present study was carried out to determine the efficacy o f Boron Neutron Capture Therapy (BNCT) for intracerebral melanoma usin g nude rats, the human melanoma cell line MRA 27, and boronophenylalan ine as the capture agent. Methods and Materials: Pharmacokinetic and t issue distribution studies: MRA 27 cells (2 X 10(5)) were implanted in tracerebrally, and 30 days later, 120 mg of B-10-L-BPA were injected i ntraperitoneally into nude rats. Therapy experiments: Thirty days foll owing implantation, tumor bearing rats were irradiated at the Brookhav en 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 mu g/g respectively. Therapy experiments: Median survival time of untreated rats was 44 days compar ed to 76 days and 93 days for those receiving physical doses of 2.73 G y and 3.64 Gy, respectively. Rats that had received both B-10-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 r eceived the highest tumor dose (10.1 Gy) survived for > 300 days and i n a replicate experiment 21% of the rats were longterm survivors (> 22 0 days). Animals that received 12 Gy in a single dose or 18 Gy fractio nated (2 Gy X 9) of gamma photons from a Cs-137 source had median surv ival times of 86 and 79 days, respectively, compared to 47 days for un treated animals. Histopathologic examination of the brains of longterm surviving rats, euthanized at 8 or 16 months following BNCT, showed n o residual tumor, but dense accumulations of melanin laden macrophages and minimal gliosis were observed. Conclusion: Significant prolongati ons 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 contemplat ed.