权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Basic Studies on Biochemical and Molecular Biological Diagnosis of Tumor Hypoxia by PET

PET诊断肿瘤缺氧的生化及分子生物学基础研究

基本信息

批准号：
17591260
负责人：
FURUKAWA Takako
金额：
$ 2.37万
依托单位：
National Institute of Radiological Sciences (2006-2007)University of Fukui (2005)
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 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591260/
关键词：
cancer cell tissue hypoxia PET acetate 腫瘍

项目摘要

Noninvasive imaging of tumor hypoxia would be a great help to predict therapy outcome and make treatment planning. Cu-diacetyl-bis (N4-methylthiosemicarbazone) (Cu-ATSM) labeled with positron-emitting Cu is a PET imaging agent which is reduced and trapped in cells under hypoxia. We examined the characteristics of high ^<64>Cu-ATSM uptake regions in mouse tumor mass formed by transplantation of several mouse tumor cells of different tissue origin. The high Cu-ATSM accumulation regions were hypovascular and consisted of tumor cells arrested in the cell cycle, with a few apoptotic cells. In contrast, the regions with high FDG accumulation were well vascularized and consisted of actively proliferating cells as well as highly hypoxic cells and dying cells from necrosis. The region of high Cu-ATSM accumulation seemed to be resistant to radiation and chemotherapy because of hypoxia and lack of vessels compared to high FDG regions where vessels are abundant and cells are proliferating. Cu-ATSM could be useful for therapy planning. It was intriguing that tumor mass contains regions with such unique characteristics in substantial volume. ^<64>Cu-ATSM, which can delineate hypoxic and cell cycle-arrested regions, may provide valuable information for cancer treatment.As for the production of Cu-64 by clinical small cyclotron and preparation of Cu-ATSM, we have successfully automated the process from the purification of Cu-64 from the target disc after bomberment to preparation of Cu-64 glycine solution, which established safe and reproducible supply of Cu-64 Cu-ATSM.Studying the characteristics of tumor cell metabolism, we found that acetate metabolism mediated by Acss2 in tumor cells was higher than in normal cells, and the metabolism was increased under hypoxia. These findings suggest a possibility that ^<11>C-acetate PET is visualizing hypoxic up-regulation of acetate metabolism in tumor cells.

无创性肿瘤乏氧显像有助于预测治疗效果和制定治疗方案。正电子发射铜标记的铜-二乙酰基-双（N4-甲基氨基硫脲）（Cu-ATSM）是一种PET显像剂，其在缺氧条件下被还原并被捕获在细胞中。我们研究了<64>通过移植几种不同组织来源的小鼠肿瘤细胞形成的小鼠肿瘤块中高Cu-ATSM摄取区域的特征。高Cu-ATSM积聚区域是少血管的，并且由在细胞周期中停滞的肿瘤细胞和少量凋亡细胞组成。相反，高FDG积聚的区域血管化良好，由活跃的增殖细胞以及高度缺氧的细胞和坏死的垂死细胞组成。与血管丰富且细胞增殖的高FDG区域相比，高Cu-ATSM积累的区域似乎对放疗和化疗具有抗性，因为缺氧和缺乏血管。Cu-ATSM可用于治疗计划。令人感兴趣的是，肿瘤块在相当大的体积中包含具有这种独特特征的区域。Cu-ATSM<64>能描绘细胞缺氧和细胞周期阻滞区域，为肿瘤治疗提供有价值的信息，在临床小型回旋加速器生产Cu-64和制备Cu-ATSM方面，我们成功地实现了从轰击后靶盘中Cu-64的纯化到Cu-64甘氨酸溶液制备的自动化过程，研究肿瘤细胞代谢特点，发现肿瘤细胞中Acss 2介导的乙酸代谢高于正常细胞，且缺氧时代谢增强。这些发现表明，13 <11>C-乙酸PET可能可视化肿瘤细胞中乙酸代谢的缺氧上调。