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

Abstract

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.

Dose-Dependent Suppression of Human Glioblastoma Xenograft Growth by Accelerator-Based Boron Neutron Capture Therapy with Simultaneous Use of Two Boron-Containing Compounds

“…However, due to this nature, BPA might not accumulate efficiently in resting tumor cells, thus limiting its effective use [ 39 , 58 ]. BSH, on the other hand, penetrates tumor tissue through fenestrated capillaries by adopting the enhanced permeability and retention (EPR) effect [ 59 , 60 ] and thus can provide non-selective homogenous 10 B distribution in tumor tissue and tumor vessels, even while unable to pass the BBB. The issue of overcoming the BBB by using various additional chemical agents was addressed in several fundamental studies [ 60 , 61 , 62 , 63 , 64 , 65 ]; however, BPA and BSH co-administration tends to be more effective in reaching higher 10 B tumor levels, as these drugs can synergistically reinforce individual weaknesses.…”

Perspectives of boron-neutron capture therapy of malignant brain tumors

“…The injection of L-phenylalanine prior to the injection of BPA may be one of the ways of enhancing its selectivity and leads to a reduction of BPA's accumulation in normal brain tissues compared to tumor tissues [12]. Also, the increasing accumulation of BSH in the brain tumor is marked by simultaneous injection of buthioninesulfoximine (buthioninesulfoximine-BSO) [13].…”