^131I标记抗前列腺干细胞抗原单克隆抗体治疗裸鼠原位人前列腺癌种植瘤  

The experimental study of ^131I labeling prostate stem cell antigen monoclonal antibody in the treat-ment of nude mice bearing orthotopic implantation of prostate carcinomar

作　　者：冯帆[1] 于胜强[1] 林春华[1] 吴吉涛[1] 王科[1] 孙德康[1] 崔玉朋[1] 杨典东[1] 高振利[1] 

机构地区：[1]青岛大学医学院附属烟台毓璜顶医院泌尿外科,烟台264000

出　　处：《中华实验外科杂志》2014年第4期799-801,共3页Chinese Journal of Experimental Surgery

基　　金：山东省科技发展计划项目（2011GGH21841）

摘　　要：目的探讨^131I标记抗前列腺干细胞抗原单克隆抗体（^131I-PSCA-McAb）对裸鼠原位人前列腺癌种植瘤的治疗效果。方法选取鼠龄及体积相近的BALB/c裸鼠36只，随机分为2组，分别建立激素依赖性前列腺癌细胞株（LNCap细胞）与激素非依赖性前列腺癌细胞株（PC3细胞）裸鼠前列腺癌原位种植模型。每组裸鼠再随机分为3组，分别静脉注射^131I-PSCA-McAb（实验组）、PSCA-McAb（单抗对照组）及^131I（碘对照组）各200txg，在给药后不同时间点应用单光子发射计算机断层成像技术（SPECT）观察药物聚集情况。给药48h后处死裸鼠，利用原位末端转移酶标记法（TUNEL）比较肿瘤体内凋亡水平的差异。结果（1）成功建立裸鼠原位前列腺癌种植模型，肿瘤生长良好；（2）^131I-PSCA-McAb经静脉注射后在实验组裸鼠前列腺种植瘤内聚集，在不同时段载瘤裸鼠显影均良好，两组肿瘤与对侧正常组织（T/NT）的放射性比值均在注射8h后达到峰值，分别为4．37±0．76（LNCap实验组）、4．21±0．71（PC3实验组）；（3）TUNEL检测显示阳性率LNCap细胞实验组〉单抗对照组〉碘对照组，PC3细胞实验组〉单抗对照组〉碘对照组；LNCap实验组和PC3实验组间阳性率差异无统计学意义（P〉0．05）。结论成功建立裸鼠原位前列腺癌种植模型，^131I-PSCA-McAb对裸鼠激素依赖性及激素非依赖性前列腺癌原位种植瘤均有显著的治疗效果。Objective To study the distribution, radioimmunoimaging and anti-tumor effect of ^131I labeling prostate stem cell antigen monoclonal antibody （^131I-PSCA-McAb） in nude mice bearing orthotopic implantation of prostate carcinoma. Methods Thirty-six male nude mice were randomly divided into 2 groups： LNCap cell group （androgen dependent prostate cancer） and PC3 cell group （androgen independent prostate cancer）. Each group were then subdivided into 3 subgroups： experimental group （were intrave noused 1311-PSCA-McAb 200 μg）, monoclonal control group （were intravenoused PSCA-McAb 200 μg）, iodic control group （ were intravenoused 1311 200 μg）. Continuous images of nude mice bearing LNCap cell and PC3 cell were carried out respectively at 1, 4, 8, 12 and 24 h after drugs injection. Transplantation tumor images were then observed and the radioactivity ratio of tumor/non-tumor （T/NT） was calculated. 48 h later, nude mice were sacrificed and the apoptosis of tumor tissues were measured by TdT-mediated dUTP nick end labeling （TUNEL）. Results The models of nude mice bearing orthotopic implantation of prostate carcinoma were successfully established. The peak uptake of ^131I_PSCA.McAb in orthotopic tumor of prostate carcinoma was at 8h after injection with a T/NT ratio of 4.37 ± 0. 76 （LNCap cell group） and 4. 21±0. 71 （PC3 cell group） respectively. The number of TUNEL positive cells in experimental group was larger than that of the two other control groups. Conclusion ^131 I-PSCA-McAb could effectively target PSCA and inhibit the growth of tumor, therefore was a promising radioimmunotherapy radiophamaceutical for prostate carcinoma.

关 键 词：前列腺癌原位种植模型 ^131I标记抗前列腺干细胞抗原单克隆抗体 细胞凋亡 放射免疫治疗 

分 类 号：R737.25[医药卫生—肿瘤]