南方医科大学学报

南方医科大学学报 ›› 2006, Vol. 26 ›› Issue (10): 1455-1457.

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188Re-Herceptin免疫导向治疗乳腺癌的实验研究

李贵平； 张一帆； 汪勇先；   

  1. 南方医科大学南方医院核医学科； 上海第二医科大学瑞金医院核医学科； 中国科学院上海应用物理研究所放射性药物研究中心 广东广州510515； 上海200025； 上海201800；
  • 出版日期:2006-10-20 发布日期:2006-10-20
  • 基金资助:
    中国博士后科学基金资助项目(2003033345);南方医院院长基金资助项目~~

188Re-labeled herceptin inhibits proliferation of breast cancer cell line SKBR-3 in vitro

LI Gui-ping1, ZHANG Yi-fan2, WANG Yong-xian3 1Departmant of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; 2Department of Nuclear Medicine, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China; 3Radiopharmaceutical Research Center, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China   

  1. 南方医科大学南方医院核医学科； 上海第二医科大学瑞金医院核医学科； 中国科学院上海应用物理研究所放射性药物研究中心 广东广州510515； 上海200025； 上海201800；
  • Online:2006-10-20 Published:2006-10-20

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摘要： 目的以针对HER-2/neu癌基因表达蛋白为靶点的人源性单克隆抗体Herceptin作为靶向载体,制备188Re标记的放射免疫治疗剂(188Re-Herceptin),观察其在体外对HER-2/neu癌基因高表达的SKBR-3乳腺癌细胞株的靶向结合性及抗癌作用。方法188Re对Herceptin的标记采用直接标记法,取不同放射性活度的188Re-Herceptin与SKBR-3乳腺癌细胞共同培养,以MTT法测定其对单层培养的肿瘤细胞生长的抑制作用,并计算相对抑制率(IC50)。结果188Re-Herceptin在体外可明显抑制SKBR-3细胞,且其杀伤作用呈剂量依赖性;而188Re标记的正常鼠IgG(nmIgG)和188ReO4-的抑制作用较弱。188Re-Herceptin组的IC50(76.1×104Bq/L)明显低于188Re-nmIgG组(139.2×104Bq/L)和188ReO4-组175×104Bq/L。结论188Re-Herceptin具有明显的抑制体外培养SKBR-3乳腺癌细胞生长增殖的作用,可进一步用于乳腺癌的放射免疫导向治疗。 

Abstract: Objective To investigate the inhibitory effects of 188Re-labeled herceptin on the proliferation in vitro of breast carcinoma cell line (SKBR-3) overexpressing HER-2/neu proto-oncogene. Methods Herceptin was radiolabeled with 188Re through a direct labeling method. SKBR-3 cells were cultured with 188Re-Herceptin at different radioactivity doses (3.7×104 , 18.5×104, 37×104, 55.5×104 and 74×104 Bq/ml) or with 188Re-nmIgG and 188ReO4- for comparison. The cell proliferation inhibition was determined with MTT colorimetric assay. Results 188Re-Herceptin could markedly inhibit the growth of SKBR-3 cells in a radioactivity dose-dependent fashion, while the effect of 188Re-nmIgG and 188ReO4- showed rather poor inhibitory effect in vitro. The 50% inhibition doses (IC50) of 188Re-Herceptin, 188Re-nmIgG and 188ReO4- were 76.1×104 Bq/L, 139.2×104 Bq/L and 175×104 Bq/L, respectively. Conclusion 188Re-Herceptin can effectively inhibit the growth of in vitro cultured breast cancer cells overexpressing HER-2/neu, and shows much potential for clinical use in beast cancer radioimmunotherapy. 

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