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Basic study of molecular targeting agents for neutron capture therapy

中子捕获治疗分子靶向药物的基础研究

基本信息

批准号：
13671420
负责人：
MATSUMURA Akira
金额：
$ 1.54万
依托单位：
University of Tsukuba
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 2003
项目状态：
已结题

项目摘要

1) cell cycle dependency of boronated compoundsTwo boronated compounds used in clinical settings (BSH & BPA) were investigated for its cell cycle dependency. Three cell lines (9L, c&, V-79) were used. The cells were incubated with boronated compounds in logarhytymic growth phase. As the results, BSH showed little cell cycle dependency when compared to BPA by examining the boron concentration after cell sorting by cell cycle using flowcytometry. The absolute cell boron concentration was higher in BPA than BSH. Based on these findings, the clinical application of two compounds may be improved (Yoshida et al. 2002)2) The uptake mechanism of BSH into the cellsBSH is composed from the carborane cage with a thiol (-SH). We have investigated the intake of BSH into three cell lines in relationship to the depletion of Glutathione (GSH), which is a major thiol compound in the cells. By depleting the GSH using BSO, the uptake of BSH was increased in all three cell lines. The neutron irradiation r … More esulted in stronger killing effect in BSO+BSH than DSH group. The gamma irradiation resulted lower killing effect in BSO+BSH than HSO group. These results indicate that uptake mechanism of BSH may be related to thiol uptake and the BSH may serve as a radioprotectant though its effect is weak3) Basic study for gadolinium neutron capture therapy (Gd-NCT)Gd-DTPA has been widely used for MRI contrast agent for CNS disease. We have investigated a new hepatocellular MRI contrast agent (Gd-BOPTA) for possible agent for Gd-NCT. The uptake of Gd-BOYTA into normal hepatic cells are thought to be mediated by molecular mechanism of ATP binding cassette (A.BC) protein. The MRI contrast in rat brain tumor model was superior in Gd-BOPTA than Gd-DTPA and the Gd concentration was higher and retained longer in Gd-BOPTA measured by ICP-AES (Zhang et al. 2002). Based on this result, we have performed a neutron irradiation experiment in rat thigh tumor model of 9L in vivo. The result revealed that Gd-BOPTA showed better tumor control than Gd-DTPA by application of the same amount of Gd into the tumor (Matsumura et al. 2003) Less

1)硼化化合物的细胞周期依赖性研究了两种用于临床的硼化化合物（BSH和BPA）的细胞周期依赖性。使用了三种细胞系（9 L、c&、V-79）。将细胞与处于对数生长期的硼化化合物一起孵育。结果，通过使用流式细胞术检查细胞分选后的硼浓度，与BPA相比，BSH显示出很小的细胞周期依赖性。BPA中的绝对细胞硼浓度高于BSH。基于这些发现，可以改进两种化合物的临床应用（Yoshida等，2002）2）BSH进入细胞的摄取机制BSH由具有硫醇（-SH）的碳硼烷笼组成。我们已经研究了BSH摄入到三个细胞系中与谷胱甘肽（GSH）消耗的关系，谷胱甘肽是细胞中主要的巯基化合物。通过使用BSO耗尽GSH，在所有三种细胞系中BSH的摄取增加。中子辐照 ...更多信息 BSO+BSH组的杀伤作用强于DSH组。γ射线照射BSO+BSH组的杀伤作用低于HSO组。这些结果表明BSH的摄取机制可能与巯基摄取有关，BSH可能具有放射防护作用，但其作用较弱。3）钆中子俘获治疗（Gd-NCT）的基础研究我们已经研究了一种新的肝细胞MRI造影剂（Gd-BOPTA）的可能代理Gd-NCT。Gd-BOYTA进入正常肝细胞被认为是通过ATP结合盒（A.BC）蛋白的分子机制介导的。在大鼠脑肿瘤模型中，Gd-BOPTA的MRI对比度上级优于Gd-DTPA，并且通过ICP-AES测量，Gd-BOPTA中的Gd浓度更高且保留时间更长（Zhang等人，2002）。在此基础上，我们进行了中子辐照大鼠大腿肿瘤模型9 L在体实验。结果显示，通过将相同量的Gd应用于肿瘤中，Gd-BOPTA显示出比Gd-DTPA更好的肿瘤控制（Matsumura等人，2003）。