Visualization of oral cancer microenvironment using molecular imaging and its application to radiotherapy

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Cell kinetics is thought to be an important factor that significantly affects cellular radiosensitivity in solid tumors; however, it was almost impossible to technically detect its dynamics in a condition that cells are alive. It is highly speculated that cells should exhibit a different cell kinetics in tumor microenvironments from that in monolayer cultures. In this study, we examined how tumor cells show the change of cell kinetics in tumor microenvironments following irradiation, using a novel technique to visualize the cell cycle. We succeeded in visualizing the difference in radiation-induced cell kinetics between outer- and inner-layers in multicellular spheroids. Furthermore, we found that radiation-induced G2 arrest was remarkably prolonged in tumor microenvironments. Considering that cells in the cell cycle phase of G2 arrest is radiosensitive, the present findings should provide important clinical implications in a fractionated regimen.