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 10B 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 approximately 30 to approximately 70 microg 10B/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 approximately 30 to approximately 80 microg 10B/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 approximately 26 to approximately 38 microg 10B/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.
Joel
D D
DD
Medical Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Coderre
J A
JA
Micca
P L
PL
Nawrocky
M M
MM
D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D005909:Glioblastoma / Q000532:radiotherapy*; D018316:Gliosarcoma / Q000532:radiotherapy*; D007262:Infusions, Intravenous; D008657:Metabolic Clearance Rate; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D001896:Boron Compounds; D011838:Radiation-Sensitizing Agents; D010649:Phenylalanine; C033685:4-boronophenylalanine