Biodistribution of p-Boronophenylalanine in Patients with Glioblastoma Multiforme for Use in Boron Neutron Capture Therapy

OBJECTIVE: The success of boron neutron capture therapy depends on the safety and specificity of the boron delivery agent. As a preface to clinical boron neutron capture therapy of glioblastoma multiforme, a biodistribution study of intravenous p-boronophenylalanine (BPA) in patients undergoing craniotomy for resection of glioblastoma was performed. METHODS: Varying doses of intravenously administered BPA-fructose (130-250 mg BPA per kilogram of body weight) were given to patients 2 to 3 hours prior to the start of craniotomy for either suspected or known glioblastoma multiforme. Blood samples were collected over a 48-hour period for boron assay. At surgery, multiple samples of tumor, brain, and scalp were obtained for boron and histological analysis. RESULTS: Seventeen patients were studied; all but one had glioblastoma multiforme. No adverse effects from the BPA infusions were noted. The boron concentration in the blood reached a maximum at the end of the BPA infusion and was proportional to the administered dose of BPA. Normal brain concentrations of boron generally were equal to or less than that in blood. Tumor-blood boron ratios were highly variable: 1.6 ± 0.8 (mean ± standard deviation; n = 187; range, 0.3-3.5). The observed heterogeneity of BPA uptake in glioblastoma samples appears to correlate with the degree of cellularity observed on histological examination. CONCLUSION: Intravenous BPA administration up to a dose of 250 mg/kg is safe and well tolerated. BPA uptake in surgical samples of glioblastoma tissue is variable and may depend on the fraction of viable tumor cells in the individual sample. Further clinical studies using BPA as a boron delivery agent for boron neutron capture therapy of glioblastoma multiforme appear warranted.