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Development of novel evaluation system and radiopharmaceutical for prediction of tumor treatment effect ; especially oxygen effect of tumor therapy

开发用于预测肿瘤治疗效果的新型评估系统和放射性药物；

基本信息

批准号：
17390331
负责人：
MAGATA Yasuhiro
金额：
$ 6.46万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
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-17390331/
关键词：
Tumor Oxygen effect PET SPEC Cell line membrane potential animal PDT

项目摘要

The tumor treatment by radiation therapy or photo dynamic therapy (PDT) is limited by several biological factors such as tumor size, angiogenesis surrounding the tumor, blood flow. Especially, it is well known that oxygen concentration in the tumor circumstance affects on these therapies and the success rate decreases in the anoxia region. Although many researches have been performed concerning the oxygen effect, it is difficult to generalize the effect by clinical category of the tumor due to a large individual variation. Therefore, it is expected that prediction of the tumor therapy is useful for decision making of therapy planning or prognosis by the therapy. On these basis, we laid a plan to establish a novel evaluation system for prediction of tumor therapy by nuclear medicine technique in this project.An evaluation system of oxygen concentration in the tumor in vivo was established using an oxymap. PDT therapy is strongly affected by oxygen concentration in the circumstance of the tumor. We selected a novel compound for PDT therapy from a chemical compound library by in silico estimation and confirmed that this compound irradiates a single state oxygen. Because In vitro experiments indicated that this compound kills tumor cells by laser irradiation, this compound or this structure is expected to be a key compound for a new PDT drug. In order to synthesize a novel peptide imaging agent labeled with a positron emitting nuclide, automatic synthesis system of F-18-SFB was established. GPR54 has been reported to relate tumor metastasis ability. We achieved application of this labeling probe to F-18-TOM80 which binds to GPR54. Moreover, consecutive SPECT and PET imaging method was established using a small animal trimodality imaging system which was installed in 2006. Combination of these results will be useful for tumor imaging study in the future.

放射治疗或光动力疗法(PDT)治疗肿瘤受到多种生物学因素的限制，如肿瘤大小、肿瘤周围血管生成、血流等。特别是，众所周知，肿瘤环境中的氧气浓度会影响这些治疗方法，缺氧区的成功率会降低。虽然已有许多关于氧效应的研究，但由于个体差异很大，很难根据肿瘤的临床类别来概括其影响。因此，对肿瘤治疗的预测有望对治疗计划或预后的决策有所帮助。在此基础上，我们制定了建立核医学技术预测肿瘤治疗效果的新评价体系的方案，并利用氧图建立了体内肿瘤氧浓度评价体系。光动力疗法受到肿瘤环境中氧气浓度的强烈影响。我们从化合物库中选择了一种用于PDT治疗的新化合物，并证实该化合物照射的是单态氧。由于体外实验表明，这种化合物可以通过激光照射杀死肿瘤细胞，因此这种化合物或这种结构有望成为PDT新药的关键化合物。为了合成一种新型正电子发射核素标记的多肽显像剂，建立了F-18-SFB的自动合成系统。GPR54已被报道与肿瘤转移能力有关。我们实现了该标记探针在与GPR54结合的F-18-TOM80上的应用。此外，利用2006年安装的小动物三通道成像系统，建立了连续的SPECT和PET成像方法。这些结果的结合将对未来的肿瘤影像研究有所帮助。