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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)含硼化合物的细胞周期依赖性研究了临床使用的两种含硼化合物（BSH和BPA）的细胞周期依赖性。使用三种细胞系（9L, c&, V-79）。在对数生长期用含硼化合物孵育细胞。结果表明，通过流式细胞术检测细胞周期分选后的硼浓度，BSH与BPA的细胞周期依赖性较小。细胞中BPA的绝对硼浓度高于BSH。基于这些发现，这两种化合物的临床应用可能会得到改善（Yoshida et al. 2002）2) BSH进入细胞的摄取机制由碳硼烷笼与巯基（-SH）组成。我们研究了三种细胞系摄入谷胱甘肽与谷胱甘肽（GSH）消耗的关系，谷胱甘肽是细胞中主要的硫醇化合物。通过使用BSO消耗GSH， BSH的摄取在所有三个细胞系中都增加了。中子辐照对BSO+BSH的杀伤作用强于DSH组。γ辐射对BSO+BSH的杀伤作用低于HSO组。这些结果提示，BSH的摄取机制可能与巯基摄取有关，虽然BSH的作用较弱，但可能具有放射保护剂的作用。钆中子俘获治疗（Gd-NCT）的基础研究Gd-DTPA已广泛用于中枢神经系统疾病的MRI造影剂。我们研究了一种新的肝细胞MRI造影剂（Gd-BOPTA）作为Gd-NCT可能的造影剂。正常肝细胞对Gd-BOYTA的摄取被认为是通过ATP结合盒（A.BC）蛋白的分子机制介导的。Gd- bopta在大鼠脑肿瘤模型中的MRI对比优于Gd- dtpa，且ICP-AES测定的Gd- bopta中Gd浓度更高，保留时间更长（Zhang et al. 2002）。在此基础上，我们对9L大鼠大腿肿瘤模型进行了体内中子辐照实验。结果表明，Gd- bopta比Gd- dtpa更能控制肿瘤（Matsumura et al. 2003）