Abstract
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 (BSO2H), 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.
Footnotes
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↵1 Current address: Department of Drug Metabolism, Merck & Co., Inc., WP75A-203, P.O. Box 4, West Point, PA 19486.
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This work was partially supported by Grant DE-FG02-95EF62059 from the United States Department of Energy. The mass spectrometers were purchased by a grant from the Hayes Investment Fund of the Ohio Board of Regents.
- Abbreviations used are::
- BNCT
- boron neutron capture therapy
- BSH
- sodium borocaptate
- ESI-MS
- electrospray ionization mass spectrometry
- BSOH
- BSH sulfenic acid
- BSO2H
- BSH sulfinic acid
- BSSB
- BSH disulfide
- BSOSB
- BSH thiosulfinate
- BSH-CYS
- BSH-S-cysteine conjugate
- TBA
- tetrabutylammonium
- TPA
- tetrapentylammonium
- TOF
- time of flight
- MS-MS
- tandem mass spectrometry
- CID
- collision-induced disassociation
- Received July 17, 2001.
- Accepted September 14, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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