Boron Neutron Capture Therapy of Brain Tumors: Investigation of Urinary Metabolites and Oxidation Products of Sodium Borocaptate by Electrospray Ionization Mass Spectrometry

• Published in: Drug metabolism and disposition Vol. 29; no. 12; pp. 1588 - 1598
• Main Authors: Gibson, C R, Staubus, A E, Barth, R F, Yang, W, Kleinholz, N M, Jones, R B, Green-Church, K, Tjarks, W, Soloway, A H
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.12.2001
• Subjects: Biological and medical sciences; Biotransformation; Borohydrides - pharmacokinetics; Borohydrides - urine; Boron Neutron Capture Therapy; Brain Neoplasms - metabolism; Brain Neoplasms - radiotherapy; Cysteine - metabolism; Cysteine - urine; General pharmacology; Glioma - metabolism; Glioma - radiotherapy; Humans; Medical sciences; Other treatments; Oxidation-Reduction; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Spectrometry, Mass, Electrospray Ionization; Sulfhydryl Compounds - pharmacokinetics; Sulfhydryl Compounds - urine; Treatment. General aspects; Tumors; Antineoplastic agent; Human; Urine; Nervous system diseases; Metabolite; Spraying; Neutron capture; Malignant tumor; Metabolism; Electrospray; Chemical ionization; Sodium borocaptate(10B); Malignant glioma; Electric field; Treatment; Central nervous system disease; Boron Isotopes; Mass spectrometry; Boron neutron capture therapy
• ISSN: 0090-9556; 1521-009X

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 nuclei. The purpose of the present study was to determine what urinary metabolites, if any, could be detected in patients with brain tumors who were given 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. Electrospray ionization mass spectrometry has been used to investigate possible urinary metabolites of BSH. Chemical and instrument conditions were established to detect BSH and its possible metabolites in both positive and negative 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 acid (BSO 2 H), BSH disulfide (BSSB), BSH thiosulfinate (BSOSB), and a BSH- S -cysteine conjugate (BSH-CYS). Although BSH has been used clinically for BNCT since the late 1960s, this is the first report of specific biotransformation products following administration to patients. Further studies will be required to determine both the biological significance of these metabolites and whether any of these accumulate in significant amounts in brain tumors.