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) 硼化合物的细胞周期依赖性研究了临床环境中使用的两种硼化合物(BSH和BPA)的细胞周期依赖性。使用了三种细胞系(9L、c&、V-79)。结果，通过使用流式细胞仪按细胞周期分选后的硼浓度，与 BPA 相比，BSH 表现出较小的细胞周期依赖性。BPA 中的绝对细胞硼浓度较高。基于这些发现，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BSH 由带有硫醇（-SH）的碳硼烷笼组成。研究了三种细胞系摄入 BSH 与谷胱甘肽 (GSH) 消耗的关系，谷胱甘肽是细胞中的主要硫醇化合物。所有三种细胞系中 BSH 的摄取均增加，BSO+BSH 组的杀伤作用强于 DSH 组，γ 照射导致 BSO+BSH 的杀伤作用低于 HSO 组。 BSH的作用机制可能与硫醇摄取有关，虽然作用较弱，但BSH可以作为放射防护剂3）钆中子俘获治疗的基础研究(Gd-NCT)Gd-DTPA 已广泛用于 CNS 疾病的 MRI 造影剂我们研究了一种新型肝细胞 MRI 造影剂 (Gd-BOPTA) 作为 Gd-NCT 的可能吸收剂。肝细胞被认为是由 ATP 结合盒 (A.BC) 蛋白的分子机制介导的。大鼠脑肿瘤模型中的 MRI 对比度优于 Gd-BOPTA。 ICP-AES 测得的 Gd-DTPA 和 Gd-BOPTA 中的 Gd 浓度更高且保留时间更长（Zhang et al. 2002）基于此结果，我们在 9L 体内大鼠大腿肿瘤模型中进行了中子照射实验。结果表明，通过将相同量的 Gd 应用于肿瘤，Gd-BOPTA 比 Gd-DTPA 表现出更好的肿瘤控制效果 (Matsumura et al. 2003) Less

项目成果

期刊论文数量（30）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Tsuchiya Y: "Imaging of rabbit VX-2 hepatic cancer by cold and thermal neutron radiography"Jpn J Appl Phys. 42. 7151-7153 (2003)

土屋Y：“通过冷热中子射线照相对兔VX-2肝癌进行成像”Jpn J Appl Phys。

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Zhang T, Matsumura, Nose T, et al.: "Comparison of two Brain Tumor-Localizing MRI Agents : GD-BOPTA and GD-DTPA. -The study of Magnetic Resonance Imaging and Inductively Coupled Plasma Atomic Emission Spectroscopy with Rat Brain tumors"American Journal of

张 T、Matsumura、Nose T 等人：“两种脑肿瘤定位 MRI 药物的比较：GD-BOPTA 和 GD-DTPA。-磁共振成像和电感耦合等离子体原子发射光谱对大鼠脑肿瘤的研究”

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Shibata Y, Matsumura A, Nose T, et al.: "Competitive uptake of porphyrin and LDL via the LDL receptor in glioma cell lines : flow cytometric analysis"Neuro-oncology. 166. 79-87 (2001)

Shibata Y、Matsumura A、Nose T 等人：“神经胶质瘤细胞系中通过 LDL 受体竞争性摄取卟啉和 LDL：流式细胞术分析”神经肿瘤学。

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高野晋吾, 坪井康次, 松村明ら: "悪性グリオーマに対するPAV(Procarbazine, ACNU, Vincristine)療法の効果"Neuro-oncology. 11. 45-50 (2001)

Shingo Takano、Koji Tsuboi、Akira Matsumura 等人：“PAV（丙卡巴嗪、ACNU、长春新碱）治疗对恶性神经胶质瘤的影响”《神经肿瘤学》11. 45-50 (2001)。

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Matsumura A., Nose T. et al.(分担): "Clinical protocol using new neutron irradiation facility(JRR4) at JAERI. In : Frontiers in Neutron Capture Therapy Vol.1, pp283-287"Hawthrone MF, Shelly K, Wiersema RJ eds, ., Plenum Press, New York. 1469 (2001)

Matsumura A.、Nose T. 等人（贡献者）：“JAERI 使用新型中子辐照设施 (JRR4) 的临床方案。见：中子捕获疗法前沿，第 1 卷，第 283-287 页”Hawthrone MF、Shelly K、Wiersema RJ 编辑，Plenum 出版社，纽约 1469 (2001)。