权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Boron neutron capture therapy for malignant glioma in the combination of BSH and BPA

BSH 和 BPA 组合的硼中子俘获疗法治疗恶性胶质瘤

基本信息

批准号：
13671438
负责人：
KAGEJI Teruyoshi
金额：
$ 2.05万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671438/
关键词：
BNCT malignant glioma BSH BPA

项目摘要

The present report evaluates as a coperative study in Europe and Japan the pharmacokinetics and boron uptake of sodium borocaptate (BSH) and p-dihydroxyboryl phenylalanine (BPA), which has been introduced clinically as a boron carrier for boron neutron capture therapy (BNCT) in patients with glioblastoma.First, we evaluated the BSH pharmacokinetics and boron uptake clmically in 56 patients with glioblastoma after BSH intravenous infusion. For BNCT with BSH after intravenous infusion, The pharmacokinetics and boron uptake study confirm that the planned neutron irradiation after intravenous BSH infusion appears to be optimal around 12-19 hours after the infusion.Second, we analyzed the subcellular biodistrubution of BSH in a rat glioma model using immunohistichemical approach in a C6 glioma model.The Wister rats were used for this experiment. An intracerebral injection of 5.0 x 106 C6 glioma cells was introduced into the region of cerebral hemishere. Fifty mg 10B/kg BSH was infused to the rats intravenously two weeks after implantation. Host rats were divided into six groups according to the sampling time: 1hr, 4hrs, 8hrs, 16hrs, 24hrs, 48hrs. After the start of BSH infusion, Immunohistochemical study was carried out using anti-BSH antibody. Boron was already found in a whole cell one hour after BSH infusion, and then seemed to collect in cell nuclei around eight to 16 hours after infusion. It was recognized in tumor cells still 48 hours after infusion.In the case of BPA, it has been reported that neutron radiation is optimal after 1 hour after BPA infusion. This study lead that BSH is infused 12-15 hours before, and BPA is infused 1 hour before neutron irradiation to achieve the optimal clinical results in the combination of BSH and BPA.

本研究首先对56例胶质母细胞瘤患者静脉滴注硼硫钠（BSH）后的BSH药代动力学和硼摄取量进行了临床评价。对于BNCT，BSH静脉输注后的药代动力学和硼摄取研究证实，BSH静脉输注后12-19小时的计划中子照射似乎是最佳的。其次，我们在大鼠C6胶质瘤模型中用免疫组织化学方法分析了BSH在大鼠胶质瘤模型中的亚细胞生物分布。将5.0 × 106个C6胶质瘤细胞的脑内注射引入大脑半裂区域。植入后2周，大鼠静脉输注10 B/kg BSH 50 mg。按取材时间分为1h、4 h、8h、16 h、24 h、48 h六组。开始BSH输注后，使用抗BSH抗体进行免疫组织化学研究。在BSH输注后一小时，在整个细胞中已经发现了硼，然后似乎在输注后8至16小时左右在细胞核中聚集。输注后48小时，它仍在肿瘤细胞中被识别。就BPA而言，据报道，BPA输注后1小时后，中子辐射是最佳的。本研究提出在中子照射前12-15小时输注BSH，在中子照射前1小时输注BPA，以达到最佳的临床效果。