Control of intracerebral gliosarcomas in rats by boron neutron capture therapy with p-boronophenylalanine

Abstract

Boron neutron capture therapy (BNCT) of transplanted intracerebral GS-9L rat gliosarcomas was effected by irradiation at a nuclear reactor, primarily with thermal neutrons, after two intragastric doses of p-boronophenylalanine (BPA). At the time of BNCT, tumor 10B levels were approximately 40 micrograms 10B/g with tumor:blood and tumor:brain 10B concentration ratios of about 3.3:1 and 3.9:1, respectively. This resulted in calculated doses to tumor that were approximately 2.3-fold greater than those to normal brain parenchyma and brain vascular endothelium within the treatment volume. Approximately 75% of the tumor dose resulted from the 10B(n,alpha)7Li nuclear reaction. The median survival of untreated rats (n = 20) was 20 days after initiation of tumors. Reactor irradiation only (no BPA) increased the median survival to 25 days (n = 25). None of the rats in the untreated or irradiation-only groups survived longer than 34 days after initiation of tumors. Two BNCT dose levels were used: 8.9 Gy (19.3 Gy x relative biological effectiveness, or Gy-eq) and 13.4 Gy (29.0 Gy-eq). The median post-BNCT survivals of BPA-treated rats in the 8.9-Gy (n = 16) and 13.4-Gy (n = 12) groups were 60 and 120 days, respectively, including seven long-term (greater than 12 months) survivors at 8.9 Gy and six long-term (greater than 5 months) survivors at 13.4 Gy. Survival times following BPA-based BNCT (either 8.9 or 13.4 Gy) were significantly longer than those following 250-kVp X-ray doses of 15 Gy (n = 24), 22.5 Gy (n = 32) or 30 Gy (n = 26).