Development of Nuclear Medicine Modality for Selecting Cancer Therapy and for Predicting Therapeutic Efficacy from Molecular Biological Points of View

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The purpose of this study is to find the nuclear medicine modality for selecting cancer therapeutic methods and for predicting the therapeutic efficacy from the molecular biological points of view.Using the human epidermoid carcinoma, KB-31 and KB-G2 that was transfected with mdr gene into KB-31, carried out the in vitro experiments. For the scintigaphical finding, Tc-99m-MIBI and I-125 labeled anti-P-glycoprotein, the expression of mdr. The in vitro-experimental results were;The more mdr was expressed, that is the more P-glycoprotein was present in the cell, the less Tc-99m-MIBI was accumulated, while the more I-125-anti-P-glycoprotein was taken up into the cell.The effects of several chemotherapeutic agents, multidrug-resistance (MDR) modifiers, antibody against P-glycoprotein, and antisense against mdr were evaluated by using Tc-99m-MEBI and I- 125-anti-P-glycoprotein.In vivo experiments were carried our by using athymic mice bearing with KB-31 in one thigh and KB-G2 in another. In vivo-experimental results were;Mice were injected with Tc-99m-MIBI and it was found that Tc-99m was localized in the KB-31 xenografts and not in the KB-G2 ones.Mice were treated with MDR-reversing agents Mowed by injection of Tc-99m-MIBI. Tc-99m accumulation in the KB-G2 xenografts was recovered, but not completely. The side effects of reversing agents on the normal organs could be predicted from the biodistribution of Tc-99m-MIBI before its clinical symptom was appeared.In conclusion, Tc-99m-MIBI scintigraphy is a feasible modality to select which tumors are multidrug resistances, especially the expression of mdr gene, and to choose adequate reversing agents and protocol, and then to predict their effects