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

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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.