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 multiforme 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 significantly improving the therapeutic gain of BNCT. The effects of total dose, infusion time, and route of administration of BPA on tumor and blood boron concentrations were studied in rats bearing the 9L gliosarcoma. Increasing the 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 concentration from similar to 30 to similar to 70 mu g B-10/g, with a constant T : B boron concentration ratio of about 3.7 : 1. Similarly, extension of the infusion time from 2 to 6 h, at a constant dose-rate of 125 mg BPA/kg/h, resulted 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 from similar to 26 to similar to 38 mu g B-10/g with a corresponding increase 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.