Development of a new tumor seeking compound for neutron capture therapy

开发用于中子捕获疗法的新型肿瘤寻找化合物

• 批准号: 07557091
• 负责人: MATSUMURA Akira
• 金额: $ 3.71万
• 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 (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557091/
• 关键词: Boron neutron capture therapy; porphyrin; glioblastoma; brain neoplasm; radiation therapy; alpha particle; 中性子補捉療法

Three types of boronated manganese metalloporphyrin (STA-BX900, STA-BX909, STABX910) for neutron capture therapy has been developed.Results1.In vivo boron concentration study revealed highest tumor boron concentration in STA-BX909 followed by STA-BX900 and STA-BX910 24 hours after intravenous injection of 0.05mmol/kg dose. This tendency was correlated with the liver boron concentration. From this result, STA-BX909 was chosen for further radiobiological study.2.In vitro boron concentration analysis : In the cultured 9L gliosarcoma cell line, the boron concentration was stable with BSH added condition medium even after 24 hours. STA-BX909 showed increase in boron concentration as a function of time. In BSH,the intracellular boron concentration may be dependent on the medium boron concentration. STA-BX909 progressively accumulated in tumor cells and the increase of boron concentration indicated an active uptake mechanism.3.Neutron irradiation revealed also stronger biological effect with STA-BX909 than BSH and least with neutron irradiation without boron compound.As conclusions, boronated metalloporphyrin is a potential boron carrier for boron neutron capture therpay for malignant brain tumors. Further basic research is warranted to develop a clinically applicable drug.

结果1.体内硼浓度研究显示，在静脉注射0.05 mmol/kg剂量后24小时，肿瘤硼浓度最高的是STA-BX909，其次是STA-BX900和STA-BX910。这一趋势与肝脏中的硼浓度有关。2.体外硼浓度分析：在培养的9L胶质肉瘤细胞系中，加入BSH的条件培养液中，即使在培养24小时后，硼浓度仍保持稳定。STA-BX909显示硼浓度随时间增加。在BSH中，细胞内的硼浓度可能依赖于介质中的硼浓度。STA-BX909在肿瘤细胞内逐渐蓄积，且硼浓度的增加表明其具有主动摄取机制。3.中子照射显示，STA-BX909的生物学效应也比BSH强，而不含硼化合物的中子照射的生物学效应最小。结论：含硼金属卟啉是一种潜在的硼载体，可用于脑肿瘤的硼中子俘获热疗。有必要进行进一步的基础研究，以开发出临床适用的药物。

项目成果

A. Matsumura: "Gadolinium-, Boron-porphyrin derivatives for neutron capture therapy. MRI and ICP study using 9L rat Model." Sixth International Symposium on NCT for Cancer. 99 (1994)

A. Matsumura：“用于中子捕获疗法的钆、硼卟啉衍生物。使用 9L 大鼠模型进行 MRI 和 ICP 研究。”

Yamamoto, T.: "Incidence of Apoptosis in Neutron Capture Therapy Using Boron-Porphyrin Compound(STA-BX909).Recent Progress of Photodynamic Therapy" Proceedings of the 7th Annual Conference of JCIPA.Ionics,Tokyo, 131-135 (1997)

Yamamoto, T.：“使用硼卟啉化合物 (STA-BX909) 的中子捕获疗法中细胞凋亡的发生率。光动力疗法的最新进展”JCIPA 第七届年会记录。Ionics，东京，131-135 (1997)

Matsumura A: "A Basic Study for Development of Boron-porphyrin Compound for Neutron Capture Therapy." KURRI Progress Report 1996, Research Reactor Institute, Kyoto University, Osaka. 145 (1997)

Matsumura A：“用于中子捕获疗法的硼卟啉化合物开发的基础研究”。

Matsumura, A.: "A basic Study for Development of Boron-Porphyrin Compound for Neutron Capture" KURRI Progress Report 1996,The Research Reactor Insitute,Kyoto University eds, 145 (1997)

Matsumura, A.：“用于中子俘获的硼卟啉化合物开发的基础研究”KURRI 进展报告 1996，研究堆研究所，京都大学编辑，145 (1997)

Matsumura A: "Mn-Metalloporphyrin Conjugated with Gd-DTPA (Gd-ATN10) : Tumor Enhancement Agent for Magnetic Resonance Imaging." Neurol Med Chir (Tokyo). 37 (4). 327-331 (1997)

Matsumura A：“Mn-金属卟啉与 Gd-DTPA (Gd-ATN10) 结合：用于磁共振成像的肿瘤增强剂。”