Research on a new internal radiation therapy agent targeting for hypoxic tumors.

针对缺氧肿瘤的新型体内放射治疗剂的研究。

基本信息

批准号：
14370274
负责人：
FUJIBAYASHI Yasuhisa
金额：
$ 8.83万
依托单位：
University of Fukui (2004)福井医科大学 (2002-2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370274/
关键词：
Cu-64 beta emitter cyclotron tumor internal radiation therapy hypoxia hypoxia Hypoxia

项目摘要

Intratumoral distribution of [Cu-64]Cu-diacetyl-bis (N4-methylthiosemicarbazone) (^<64>Cu-ATSM) and fluorine-18 2-fluoro-2-deoxyglucose (^<18>FDG) in mice bearing tumors of four different origins, LLC1, Meth-A, B16 and colon26, were compared to the immunohistochemical staining for proliferating cells (Ki67), blood vessels (CD34 or von Willebrand Factor(vWF)) and apoptotic cells (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method). With all the cell lines, ^<64>Cu-ATSM and ^<18>FDG were distributed to different regions of the tumor mass. The immunohistochemical study demonstrated that the high ^<64>Cu-ASTM uptake regions were hypovascular and consisted of tumor cells arrested in cell cycle, while the high ^<18>FGD uptake regions were hypervascular and consisted of proliferating cells. Through our study, it was revealed that one tumor mass contains two regions of different characteristics, which can be distinguished by ^<64>Cu-ATSM and ^<18>FDG. Since hypoxia and cell cycle arrest are critical factors to reduce the sensitivity of tumor to radiation and conventional chemotherapy, regions with such characteristics in tumor should be treated intensively as one of the primary targets. ^<64>Cu-ATSM which can delineate hypoxic and cell cycle arrested regions in tumors can provide valuable information for cancer treatment as well as the possibility to treat such regions directly as an internal radiotherapy reagent.

[Cu-64]Cu-二乙酰基-双(N4-甲硫缩氨基脲)(^ 64 Cu-ATSM)和氟-18 2-氟-2-脱氧葡萄糖(^ 18 FDG)在携带肿瘤的小鼠中的瘤内分布将四种不同来源（LLC1、Meth-A、B16 和 colon26）与增殖细胞的免疫组织化学染色进行比较(Ki67)、血管（CD34 或血管性血友病因子 (vWF)）和凋亡细胞（末端脱氧核苷酸转移酶 (TdT) 介导的 dUTP 缺口末端标记 (TUNEL) 方法）。对于所有细胞系， 64 Cu-ATSM和 18 FDG分布到肿瘤块的不同区域。免疫组织化学研究证明，高^ 64 Cu-ASTM摄取区域是缺乏血管的，并且由细胞周期停滞的肿瘤细胞组成，而高^ 18 FGD摄取区域是富含血管的，并且由增殖细胞组成。通过我们的研究，发现一个肿瘤块包含两个不同特征的区域，可以通过^<64>Cu-ATSM和^<18>FDG来区分。由于缺氧和细胞周期停滞是降低肿瘤对放射和常规化疗敏感性的关键因素，因此肿瘤中具有此类特征的区域应作为主要靶点之一进行强化治疗。 ^ 64 Cu-ATSM可以描绘肿瘤中的缺氧和细胞周期停滞区域，可以为癌症治疗提供有价值的信息，并且可以作为内部放射治疗试剂直接治疗这些区域。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

藤林康久: "Different mechanisms of hypoxic injury on white matter and gray matter as revealed by dynamic changes in glucose metabolism in rats"Neuroscience Letter. 353(2). 148-152 (2003)

Yasuhisa Fujibayashi：“大鼠葡萄糖代谢动态变化揭示的白质和灰质缺氧损伤的不同机制”神经科学快报 353(2) (2003)。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Basic characterization of Cu-64-ATSM as a radiotherapy agent.

Cu-64-ATSM 作为放射治疗剂的基本特性。

DOI：
发表时间：
2005
期刊：
Nuclear Medicine & Biology 32
影响因子：
0
作者：
A.Obata;S.Kasamatsu;J.S.Lewis;T.Furukawa;S.Takamatsu J.Toyohara;T.Asai;M.J.Welch;S.G.Adams;H.Saji;Y.Yonekura;Y.Fujibayashi
通讯作者：
Y.Fujibayashi

藤林康久: "Copper-64-pyruvaldehyde-bis (N^4-methylthiosemicarbazone) for the Prevention of Tumor Growth at Wound Sites following Laparoscopic Surgery"Cancer Research. 62(2). 445-449 (2002)

Yasuhisa Fujibayashi：“铜-64-丙酮醛-双（N^4-甲硫缩氨基脲）用于预防腹腔镜手术后伤口部位的肿瘤生长”癌症研究 62(2) 445-449。