Basic study of molecular targeting agents for neutron capture therapy

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)对细胞周期的依赖性。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，与双酚A相比，BSH对细胞周期的依赖性较小，通过流式细胞仪检测细胞周期分选后的硼浓度。BPA细胞内的绝对硼浓度高于BSH。基于这些发现，两种化合物的临床应用可能会得到改进(Yoshida等人。2)BSH进入细胞的摄取机制BSH是由带有硫醇(-SH)的碳硼烷笼子组成的。我们研究了三种细胞对BSH的摄取与细胞中主要的硫醇化合物谷胱甘肽(GSH)耗竭的关系。通过用BSO去除GSH，三种细胞对BSH的摄取都增加了。中子辐照r…BSO-BSH组的杀伤作用强于DSH组。γ射线照射对BSO-BSH细胞的杀伤作用低于HSO组。这些结果表明，BSH的摄取机制可能与其对硫醇的摄取有关，BSH的辐射防护作用较弱。3)Gd-NCT的基础研究Gd-DTPA已被广泛用于中枢神经系统疾病的MRI对比剂。我们研究了一种新的肝细胞磁共振造影剂(Gd-BOPTA)，作为Gd-NCT的可能造影剂。正常肝细胞对Gd-BOYTA的摄取被认为是由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对比度优于Gd-DTPA，并且Gd-BOPTA中的Gd浓度更高，保留时间更长(Zhang等人)。2002年)。基于这一结果，我们在9L大鼠大腿肿瘤模型上进行了体内中子照射实验。结果表明，在肿瘤内应用相同数量的Gd，Gd-BOPTA显示出比Gd-DTPA更好的肿瘤控制(MatSumura et al.2003年)较少

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