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 c linical boron neutron capture therapy of glioblastoma multiforme, a bi odistribution study of intravenous p-boronophenylalanine (BPA) in pati ents undergoing craniotomy for resection of glioblastoma was performed . METHODS: Varying doses of intravenously administered BPA-fructose (1 30-250 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 know n 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 multifo rme. No adverse effects from the BPA infusions were noted. The boron c oncentration in the blood reached a maximum at the end of the EPA infu sion and was proportional to the administered dose of EPA. Normal brai n concentrations of boron generally were equal to or less than that in blood. Tumor-blood boron ratios were highly variable: 1.6 +/- 0.8 (me an +/- standard deviation; n = 187; range, 0.3-3.5). The observed hete rogeneity of BPA uptake in glioblastoma samples appears to correlate w ith the degree of cellularity observed on histological examination. CO NCLUSION: Intravenous BPA administration up to a dose of 250 mg/kg is safe and well tolerated. EPA uptake in surgical samples of glioblastom a tissue is variable and may depend on the fraction of viable tumor ce lls in the individual sample. Further clinical studies using BPA as a boron delivery agent for boron neutron capture therapy of glioblastoma multiforme appear warranted.