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

本研究旨在从分子生物学的角度探索核医学模式对肿瘤治疗方法的选择和治疗效果的预测。以人表皮样癌KB-31和mdr基因转染KB-31的KB-G2进行体外实验。对于科学发现，Tc-99m-MIBI和I-125标记抗p糖蛋白，mdr的表达。体外实验结果为；mdr表达越多，即细胞中p -糖蛋白含量越多，Tc-99m-MIBI积累越少，而i- 125抗p -糖蛋白进入细胞的量越多。采用Tc-99m-MEBI和I- 125-anti- p -糖蛋白，评价几种化疗药物、多药耐药（MDR）调节剂、抗p -糖蛋白抗体和抗MDR反义抗体的疗效。用胸腺小鼠进行体内实验，一只腿携带KB-31，另一只腿携带KB-G2。体内实验结果为；给小鼠注射Tc-99m- mibi，发现Tc-99m只存在于KB-31异种移植物中，而不存在于KB-G2中。小鼠用Tc-99m-MIBI注射的耐多药逆转剂治疗。Tc-99m在KB-G2异种移植物中的积累得到恢复，但不完全恢复。在Tc-99m-MIBI出现临床症状之前，通过其生物分布可以预测逆转药物对正常器官的副作用。综上所述，Tc-99m-MIBI扫描技术是一种可行的方法，可以选择哪些肿瘤是多药耐药，特别是mdr基因的表达，选择合适的逆转药物和方案，然后预测其效果

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