Development of new measurement methods of tumor oxygenation

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It is well known that the presence of hypoxic cells in solid tumors is one of the most important cause of failure after radiation therapy and some chemotherapy regimens. Up to this time, many efforts have been made to overcome this problem. However, there is an important problem that we have no valid methods for the routine measurement of the intratumoral hypoxic fraction in patients. Previous study suggests that the hypoxic fraction differs with the tumor type, but it is not known what kind of tumor contains a high hypoxic fraction, that is refractory to strategy for radiotherapy.In this study, we have tested the possibilities to identify hypoxic fraction in tumors using two methods : the comet assay (single-cell electrophoresis assay) and detection of hypoxic cells using PET scan for Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone).The comet assay has been developed as a method for measuring DNA damage in single cells after irradiation. We have developed our own methods and image analysis system for the comet assay to identify hypoxic fractions. In vitro, we tested our system using a cultured tumor cell line. In vivo, we compared the hypoxic fractions detected by this assay with those determined by the in vivo-in vitro clonogenic assay using two rodent tumors, which exhibit different types of hypoxia : acute and chronic.In vitro, our method could differentiate hypoxic cells from oxic cells, using the parameter of tail moment. In vivo, there were good correlations between the hypoxic fractions determined by the comet assay and by the clonogenic assay, in both tumors. By comparison of the two methods in chronically hypoxic and acutely hypoxic tumors, we further confirmed that the comet assay is clinically useful for estimation hypoxic fractions of solid tumors.