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

放射治疗或光动力治疗（PDT）的肿瘤治疗受到几个生物学因素的限制，如肿瘤大小、肿瘤周围的血管生成、血流。特别是，众所周知，肿瘤环境中的氧浓度会影响这些治疗，并且在缺氧区域成功率降低。虽然对氧效应的研究较多，但由于个体差异较大，很难按肿瘤的临床类别来概括氧效应。因此，对肿瘤治疗的预测有助于治疗人员制定治疗计划或预后。在此基础上，本项目拟建立一套新的核医学肿瘤治疗预测评价体系。采用氧图法建立了肿瘤体内氧浓度评价系统。PDT治疗在肿瘤环境下受氧浓度的影响很大。我们从化学化合物库中选择了一种新的化合物用于PDT治疗，并通过硅估计证实了该化合物能照射单态氧。由于体外实验表明该化合物可通过激光照射杀死肿瘤细胞，因此该化合物或该结构有望成为新型PDT药物的关键化合物。为了合成一种新型正电子发射核素标记肽显像剂，建立了F-18-SFB的自动合成系统。据报道，GPR54与肿瘤转移能力有关。我们将该标记探针应用于与GPR54结合的F-18-TOM80。利用2006年安装的小动物三模成像系统，建立了SPECT和PET的连续成像方法。这些结果对今后的肿瘤影像学研究有一定的指导意义。

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.