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

从分子生物学角度选择癌症治疗和预测治疗效果的核医学模式的发展

• 批准号: 11670912
• 负责人: NAKAMURA Kayoko
• 金额: $ 2.18万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670912/
• 关键词: Tc-99m-MIBI; Multidrug resistance (MDR); MDR reversing; Monitoring; Prediction; P-glycoprotein; 多剤耐性; P-糖蛋白質; 核医学的手法; 悪性腫瘍; T'c-99m-MIBI; アンチセンス

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

本研究以人表皮样癌KB-31和转染mdr基因的KB-31细胞株KB-G2为研究对象，进行了体外实验研究，目的是从分子生物学角度探讨肿瘤治疗方法选择和疗效预测的核医学模式。免疫组化结果显示，Tc-99 m-MIBI和I-125标记的抗P-糖蛋白（P-glycoprotein，P-糖蛋白）可抑制mdr.体外实验结果为：多药耐药（MDR）基因表达越多，即P糖蛋白表达越多，Tc-99 m-MIBI蓄积越少，而I-125-抗P糖蛋白被摄取越多，几种化疗药物、多药耐药（MDR）修饰剂、抗P糖蛋白抗体、用~（99 m）Tc-MEBI和~（125）I-抗P-糖蛋白检测mdr和mdr反义核酸的表达。体内实验结果表明：小鼠注射Tc-99 m-MIBI后，发现Tc-99 m-MIBI定位于KB-31移植瘤，而不定位于KB-G2移植瘤。KB-G2异种移植物中的Tc-99 m蓄积恢复，但不完全恢复。在临床症状出现之前，根据99 m-MIBI的生物分布可预测逆转剂对正常器官的副作用，因此，99 m-MIBI放射学显像是筛选耐药肿瘤，特别是mdr基因表达，选择合适逆转剂和方案，预测逆转剂疗效的一种可行方法

项目成果

K. Nakamura: "Nuclear Oncology in Future"RADIOISOTOPES. 49 (1). 26-31 (2000)

K. Nakamura：“未来的核肿瘤学”放射性同位素。

K. Nakamura: "Gene and Clinical Nuclear Medicine (4)"Nucl Med in Clinic. 33 (5). 72-73 (2000)

K. Nakamura：《基因与临床核医学（4）》临床中的核医学。

中村佳代子: "遺伝子と臨床核医学(3):PCR、プライマー、アニーリング"臨床核医学. 33(3). 44-45 (2000)

Kayoko Nakamura：“基因和临床核医学 (3)：PCR、引物、退火”临床核医学 33(3)。

中村佳代子: "遺伝子と臨床核医学(2)"臨床核医学. 33. 8-10 (2000)

中村佳代子：《基因与临床核医学（2）》《临床核医学》33. 8-10 (2000)。

藤井博史, 中村佳代子, 他: "乳腺腫瘍:Tc-99m-MIBIによる診断"INNERVISION. 15. 86-89 (2000)

Hiroshi Fujii、Kayoko Nakamura 等：“乳腺肿瘤：Tc-99m-MIBI 诊断”INNERVISION 15. 86-89 (2000)。