Boron compound uptake augmentation to use for neutron capture therapy.

硼中子俘获疗法（BNCT）是使用硼（B^<10>）化合物和热中子的靶向放射疗法。硼帽酸钠（Sodium borocaptate，BSH）广泛应用于脑肿瘤的BNCT。我们报道了BSH摄取在体外与丁硫氨酸亚砜亚胺（BSO）组合时增强（Cancer Lett. 215（2004）61-67）。在这项研究中，我们研究了BSO对BSH在体内分布的影响。将9 L胶质肉瘤细胞接种于Fisher 344大鼠右腿皮下。2周后将大鼠分为BSO+组、BSO-组和未处理组（对照）。分别于注射后3 h、6 h和12 h处死大鼠，取脑、血液、皮下肿瘤、肌肉、皮肤、肝脏和肾脏等组织标本。血硼浓度测定结果：注射后3 h血硼浓度为55.2±15.0 μg/mg，注射后3 h血硼浓度为20.2± 14.0 μg/mg。BSO+组6 h为10.8 ±20.6 μg/mg。BSH组分别为8.1 ± 6.2 μg/mg、3.4 ± 0.5 μg/mg、1.3 ± 0.2 μg/mg。各组织中硼的浓度与血硼浓度成正比，由于BSO联合用药可维持体内高浓度硼水平，因此我们对大鼠腿部皮下肿瘤进行了BNCT。结果表明，BSO+组与BSO-组相比，肿瘤明显减少。总之，BSO在体内和体外联合使用可增强BSH的摄取。

Boron neutron capture therapy (BNCT) is a targeted radiation therapy using a boron (B^<10>) compound and thermal neutrons. Sodium borocaptate (BSH) is widly used for BNCT of brain tumor. We reported that BSH uptake was enhanced in combination with butionine sulfoximine (BSO) in vitro (Cancer Lett. 215 (2004) 61-67). In this study, we investigated influence of BSO on BSH distribution in vivo. 9L glicosarcoma cells were subcutaneously inoculated to right legs of Fisher 344 rats. After 2 weeks, the rats were divided into 3 groups, BSO+ group, BSO-group and untreated group (control). The rats were sacrificed at 3 hours, 6hours or 12 hours after injection, and samples of brain, blood, subcutaneous tumor, muscle, skin, liver and kidney were obtained. The results of the blood boron concentration were 55.2±15.0 μg/mg at 3 hours after injection, 20.2±14. μg/mg at 6 hours, 10.8 ±20.6 μg/mg in BSO+ group. On the other hands, in BSH only group, they were 8.1 ± 6.2 μg/rag, 3.4 ± 0.5 μg/mg, 1.3 ± 0.2 μg/mg, respectively. The boron concentration included in each tissues were in proportion to blood boron concentration.Since in vivo boron level was maintained with high concentration by BSO combination, we performed BNCT for the subcutaneous tumor which we made to the rats legs. As the result, a tumor reduced BSO+ group significantly in comparison with BSO-group.In conclusion, the uptake of BSH was enhanced in combination with BSO in vivo as well as in vitro.