BIODISTRIBUTION OF BORONOPHENYLALANINE IN PATIENTS WITH GLIOBLASTOMA-MULTIFORME - BORON CONCENTRATION CORRELATES WITH TUMOR CELLULARITY

Boron-10 (B-10) concentrations were measured in 107 surgical samples f rom 15 patients with glioblastoma multiforme who were infused with 95 atom% B-10-enriched p-boronophenylalanine (BPA) intravenously for 2 h just prior to surgery at doses ranging from 98 to 290 mg BPA/kg body w eight. The blood B-10 concentration reached a maximum at the end of th e infusion (ranging from 9.3 to 26.0 mu g B-10/g) and was proportional to the amount of BPA infused. The boron concentrations in excised tum or samples ranged from 2.7 to 41.3 mu g B-10/g over the range of admin istered BPA doses and varied considerably among multiple samples from individual patients and among patients at the same BPA dose. A morphom etric index of the density of viable-appearing tumor cells in histolog ical sections obtained from samples adjacent to, and macroscopically s imilar to, the tumor samples used for boron analysis correlated linear ly with the boron concentrations. From that correlation it is estimate d that B-10 concentrations in glioblastoma tumor cells were over four times greater than concurrent blood B-10 concentrations. Thus, in the dose range of 98 to 290 mg BPA/kg, the accumulation of boron in tumor cells is a linear function of BPA dose and the variations observed in boron concentrations of tumor specimens obtained surgically are largel y due to differences in the proportion of nontumor tissue (i.e. necrot ic tissue, normal brain) present in the samples submitted for boron an alysis. The tumor:blood B-10 concentration ratio derived from this ana lysis provides a rationale for estimating the fraction of the radiatio n dose to viable tumor cells resulting from the boron neutron capture reaction based on measured boron concentrations in the blood at the ti me of BNCT without the need for analysis of tumor samples from individ ual patients. (C) 1998 by Radiation Research Society.