Pretreatment with buthionine sulfoximine enhanced uptake and retention of BSH in brain tumor

• Published in: Applied radiation and isotopes 2014-06, Vol.88, p.86-88
• Main Authors: Yoshida, F., Yamamoto, T., Nakai, K., Zaboronok, A., Matsuda, M., Akutsu, H., Ishikawa, E., Shirakawa, M., Matsumura, A.
• Format: Article
• Language: English
• Subjects: Animals; Borohydrides - administration & dosage; Borohydrides - pharmacokinetics; Boron Neutron Capture Therapy - methods; Brain Neoplasms - metabolism; Brain Neoplasms - radiotherapy; Buthionine sulfoximine; Buthionine Sulfoximine - administration & dosage; Buthionine Sulfoximine - pharmacokinetics; Drug Synergism; Male; Metabolic Clearance Rate - drug effects; Neutron capture therapy; Organ Specificity - drug effects; Premedication - methods; Rats; Rats, Inbred F344; Sulfhydryl borane; Sulfhydryl Compounds - administration & dosage; Sulfhydryl Compounds - pharmacokinetics; Tissue Distribution - drug effects
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2014.02.025

To determine the influence of buthionine sulfoximine (BSO) on boron biodistribution after sulfhydryl borane (BSH) administration for boron neutron capture therapy, the effectiveness of the combination of BSO with sulfhydril- (BSH) and non-sulfhydril (B12H12 and BNH3) boron compounds, and the interval between BSO and BSH administration, the retention of boron in tissues have been evaluated using a 9L rat tumor model. Simultaneous administration of BSH and BSO showed significantly higher boron accumulation compared to that without BSO, however there was no difference in tissue boron level between B12H12 and BNH3 administration with BSO or without BSO. The longer interval (6h) between BSH and BSO administration related to the highest boron concentration in the brain and subcutaneous tumors compared to shorter intervals (0.5, 3h). Boron concentration in subcutaneous and brain tumors was maintained for 6 and 12h after the administration of BSH following BSO pretreatment. •Coadministration of BSH and BSO showed higher tumor boron uptake than BSH only.•Higher boron uptake was not observed after B12H12 or BNH3 administration.•The increase in tumor boron accumulation might be related to SH-groups.•BSO injection 6h before BSH showed further increase in tumor boron uptake.•High boron concentration maintained for 6 and 12h after BSH with BSO administration.