Effect of dose and infusion time on the delivery of p-boronophenylalanine for neutron capture therapy

Clinical trials of boron neutron capture therapy (BNCT) for glioblastoma mu ltiforme are currently in progress using p-boronophenylalanine (BPA) as the B-10 delivery agent. Enhancement of tumor boron uptake and/or the tumor-to -blood (T:B) boron concentration ratio would have the potential of signific antly improving the therapeutic gain of BNCT. The effects of total dose, in fusion time, and route of administration of BPA on tumor and blood boron co ncentrations were studied in rats bearing the 9L gliosarcoma. Increasing th e total dose of BPA from 250 to 1000 mg/kg, administered intravenously over a 2-h infusion period, resulted in an increase in tumor boron concentratio n from similar to 30 to similar to 70 mu g B-10/g, with a constant T : B bo ron concentration ratio of about 3.7 : 1. Similarly, extension of the infus ion time from 2 to 6 h, at a constant dose-rate of 125 mg BPA/kg/h, resulte d in an increase in tumor boron concentration from similar to 30 to similar to 80 mu g B-10/g, while, again, maintaining a constant T:B ratio of about 3.7 : 1. In contrast, intracarotid infusion of BPA for 1 h at a dose rate of 125 mg BPA/kg resulted in an increase in the tumor boron concentration f rom similar to 26 to similar to 38 mu g B-10/g with a corresponding increas e in the T:B ratio from 3.5 : 1 to 5.0 : 1. The effects of these results on the therapeutic gain potentially achievable with BNCT are discussed.