Boron Neutron Capture Therapy of Brain Tumors: Biodistribution, Pharmacokinetics, and Radiation Dosimetry of Sodium Borocaptate in Patients with Gliomas

Abstract

When tumor, blood, and normal tissue boron concentrations were taken into account, the most favorable tumor uptake data were obtained with a boron dose of 25 mg/kg body weight, 3 to 7 hours after termination of the infusion. Although blood boron levels were high, normal brain tissue boron levels were almost always lower than tumor levels. However, tumor boron concentrations were less than those necessary for boron neutron capture therapy, and there was significant intratumoral and interpatient variability in the uptake of BSH, which would make estimation of the radiation dose delivered to the tumor very difficult. It is unlikely that intravenous administration of a single dose of BSH would result in therapeutically useful levels of boron. However, combining BSH with boronophenylalanine, the other compound that has been used clinically, and optimizing their delivery could increase tumor boron uptake and potentially improve the efficacy of boron neutron capture therapy.

Boron delivery agents for neutron capture therapy of cancer

“…The major problem with both BSH and BPA is the significant variability in tumor uptake, especially in brain tumors. This was clearly demonstrated by Goodman et al [ 46 ]. in a biodistribution and pharmacokinetic study involving 20 patients with high grade gliomas.…”

Boron neutron capture therapy: Current status and future perspectives

“…It is considered that BSH uses passive diffusion through the plasma membrane to enter tumor cells [24]. BSH has a high T/N ratio with weak accumulation in tumor cells, while BPA accumulates well in tumor cells but has a low T/N ratio [25,26]. At 2 h after the intravenous administration of BPA, the maximum T/N boron concentration ratios are observed [27].…”

Towards carborane-functionalised structures for the treatment of brain cancer

“…Screening experiments [33] designed to select drugs that give favourable tumour/blood concentration ratios identified the selective tumourcell uptake of sodium dimercaptooctachlorodecaborate (1,10-Na 2 B 10 Cl 8 (SH) 2 ; compound 3, Figure 2) and sodium mercaptoundecahydrododecaborate (BSH; compound 4, Figure 2). The impetus for further studies was provided by speculation, at the time, that the capability to recognize tumour cells and to promote accumulation may be inherent to the boron cluster structure, or may be linked to ionic charge, or to a specific interaction with certain proteins.…”