Boron neutron capture therapy of brain tumors: Investigation of urinary metabolites and oxidation products of sodium borocaptate by electrospray ionization mass spectrometry

Boron neutron capture therapy (BNCT) is based on a nuclear capture reaction that occurs when boron-10, a stable isotope, is irradiated with low energy neutrons to produce high-energy alpha particles and recoiling lithium-7 nu clei. The purpose of the present study was to determine what urinary metabo lites, if any, could be detected in patients with brain tumors who were giv en sodium borocaptate (BSH), a drug that has been used clinically for BNCT. BSH was infused intravenously over a 1-h time period at doses of 26.5,44.1 , or 88.2 mg/kg of body weight to patients with high-grade brain tumors. El ectrospray ionization mass spectrometry has been used to investigate possib le urinary metabolites of BSH. Chemical and instrument conditions were esta blished to detect BSH and its possible metabolites in both positive and neg ative electrospray ionization modes. Using this methodology, boronated ions were found in patients' urine samples that appeared to be consistent with the following chemical structures: BSH sulfenic acid (BSOH), BSH sulfinic a cid (BSO2H), BSH disulfide (BSSB), BSH thiosulfinate (BSOSB), and a BSH-S-c ysteine conjugate (BSH-CYS). Although BSH has been used clinically for BNCT since the late 1960s, this is the first report of specific biotransformati on products following administration to patients. Further studies will be r equired to determine both the biological significance of these metabolites and whether any of these accumulate in significant amounts in brain tumors.