Development of specific radiation therapy targeting hypoxic cells

针对缺氧细胞的特异性放射治疗的开发

• 批准号: 17591247
• 负责人: SAKURAI Hideyuki
• 金额: $ 2.3万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591247/
• 关键词: hypoxia; radiation; treatment resistance; hypoxic marker

Hypoxic cells distributed unevenly through tumors are believed to be the primary determinants in resistance to radiation therapy and chemotherapy. It is thought that if tumors are left in a state of hypoxia for an extended period, their malignancy, in terms of proliferative or metastasizing potential, will increase due to vascular endothelial growth factor and other factors. Here, we developed a method for measuring the hypoxic state of tumors in which hypoxic cells are imaged via the hypoxic cell markers that characterize them. We then used this method as an addition to the previously developed 31P-MRS and MRI methods to develop a type of missile therapy targeting hypoxic cells, to conduct positron-based diagnosis using hypoxic cell markers labeled with nuclides such as 64Cu and 67Cu, and to develop a new method of cancer therapy through the combination of hypoxia-targeting missile therapy with a molecular-targeted drug that inhibits neoangiogenesis. As part of our experiments, we implanted SASneo cells with normal p53 and SASmp cells, which have an abnormality in p53. The SASmp cells showed a faster rate of proliferation and a greater tendency to necrotize than the SASneo cells. On injection of 67-Cu-ATSM into the caudal vein of these mice, distribution of RI at 1 and 24 hours after injection was relatively high in parenchymal organs such as the liver, kidneys, and lungs, with relative distribution rates to a plasma rate of 1 of 5.15, 2.33, and 2.32, respectively. In contrast, accumulation in the central nervous system was low, with a distribution rate of only 0.67. RI accumulation did not differ between SASmp and SASneo. Autoradiography of the excised tumors showed 67-Cu-ATSM accumulation in the peripheral portions of tumors. Further, the rate of delay in tumor growth following the injection of isotopes at therapeutic concentrations revealed that growth inhibition tended to be greater in SASneo cells than in SASmp cells.

低分化细胞在肿瘤中的不均匀分布被认为是对放射治疗和化学治疗抵抗的主要决定因素。据认为，如果肿瘤长时间处于缺氧状态，由于血管内皮生长因子和其他因素，其恶性程度（就增殖或转移潜力而言）将增加。在这里，我们开发了一种测量肿瘤缺氧状态的方法，其中缺氧细胞通过表征它们的缺氧细胞标志物成像。然后，我们使用这种方法作为对先前开发的31 P-MRS和MRI方法的补充，开发了一种靶向低氧细胞的导弹治疗，使用用核素标记的低氧细胞标记物（如64 Cu和67 Cu）进行基于正电子的诊断，并通过将低氧靶向导弹治疗与抑制新生血管生成的分子靶向药物相结合，开发了一种新的癌症治疗方法。作为我们实验的一部分，我们将SASneo细胞与正常的p53和SASmp细胞植入，SASmp细胞在p53中有异常。SASmp细胞比SASneo细胞具有更快的增殖速率和更大的坏死倾向。将67-Cu-ATSM注射到这些小鼠的尾静脉中，注射后1和24小时RI在实质器官如肝、肾和肺中的分布相对较高，相对于血浆的分布率分别为5.15、2.33和2.32。相比之下，在中枢神经系统中的蓄积较低，分布率仅为0.67。RI的积累在SASmp和SASneo之间没有差异。切除肿瘤的放射自显影显示67-Cu-ATSM在肿瘤的外周部分积聚。此外，注射治疗浓度的同位素后肿瘤生长延迟的速率显示，SASneo细胞中的生长抑制倾向于大于SASmp细胞。

项目成果

放射線医科学

放射科学

• 发表时间: 2016
• 作者: Hosono M;Hanaoka K;Ishii K;Im S;Sakaguchi K;Yagyu Y;Komeya Y;Tsuchiya N;Tatsumi Y;Matsumura I;細野 眞;細野 眞;細野 眞
• 通讯作者: 細野 眞

Effect of histologic type o recurrence pattern in radiation therapy for medically inoperable patients with stage 1 non-small cell lung cancer

组织学 o 型复发模式对无法手术的 1 期非小细胞肺癌患者放射治疗的影响

• 发表时间: 2006
• 期刊: Lung 18
• 作者: Yamada;M.;Iwabuchi;T.;Takahashi;K.;Kurahashi;C.;Higuchi;T.;Yamada;M.;Katsuyoshi Hori;Ishikawa H et al.
• 通讯作者: Ishikawa H et al.

Radiation therapy alone for stage1(UICCT1N0M0) squamous cell carcinoma of the esophagus : Indication for surgery or combined chemoradiotherapy

单独放疗治疗 1 期 (UICCT1N0M0) 食管鳞状细胞癌：手术或联合放化疗的指征

• 发表时间: 2006
• 期刊: Gastroenterology 21
• 作者: Yoneyama A;et al.;Katsuyoshi Hori;Ishikawa H et al.
• 通讯作者: Ishikawa H et al.

FDG-PET in the detection of recurrence of uterine cervical carcinoma following radiation therapy-tumor volume and FDG uptake value

• DOI: 10.1016/j.ygyno.2005.09.030
• 发表时间: 2006-03-01
• 期刊: GYNECOLOGIC ONCOLOGY
• 影响因子: 4.7
• 作者: Sakurai, H;Suzuki, Y;Nakano, T
• 通讯作者: Nakano, T

The synchronization of chemotherapy to circadian rhythms and irradiation in pre-operative chemoradiatherapy with hyperthermia for local advanced rectal cancer

局部晚期直肠癌术前热放化疗中化疗与昼夜节律和放疗的同步

• 发表时间: 2006
• 期刊: Int J Hyperthermia 22
• 作者: Kudo;K;et al.;Akio Yoneyama;Asao T et al.
• 通讯作者: Asao T et al.