抗前列腺特异膜抗原单克隆抗体的标记及在荷瘤裸鼠体内的分布研究

目的:研究125I标记的抗前列腺特异膜抗原(PSMA)单克隆抗体(125Ⅰ-Ed-5)及正常小鼠IgG(125Ⅰ-NMIgG)在荷人前列腺癌瘤裸鼠体内的分布,探讨应用125Ⅰ-Ed-5进行放射免疫显像诊断和放射免疫治疗实验性人前列腺癌的可行性.方法:建立荷人前列腺癌裸鼠移植瘤模型,用125Ⅰ标记抗PSMA单克隆抗体Ed-5和NMIgG,125Ⅰ-Ed-5和125Ⅰ-NMIgG经尾静脉注入荷瘤裸鼠体内,于注射后24、48、72、120小时分批处死,测定肿瘤和血液、肝、肺等重要脏器的单位重量放射性比值(T/NT)、各组织摄取百分比(%ID/g),研究其在荷瘤裸鼠体内的放射性分布情况.结果:125Ⅰ-Ed-5的标记率为72.3%,放射性比活度为55.2MBq/mg,放射性化学纯度是90.2%,免疫活性分数为63%.在注射125Ⅰ-Ed-5后24～120小时内,裸鼠体内肿瘤部位出现选择性放射性浓聚:各组织的T/NT比值在72h达到最高,其中肿瘤/肌肉高达6.36.而在注射125Ⅰ-NMlgG的对照组中,裸鼠体内未见放射性浓聚,呈全身均匀性分布.结论:标记后的125Ⅰ-Ed-5免疫活性没有改变,在裸鼠体内对前列腺癌移植瘤有靶向定位作用,为进一步应用125Ⅰ-Ed-5进行前列腺癌放射免疫显像和放射免疫治疗的实验研究奠定基础.

The Study on Labelling of Anti-human Prostatic Specific Membrane Antigen and Bio-distribution in Nude Mice Bearing Human Prostate Cancer

Objective: To study the bio-distribution of 125I labeled anti-human prostatic specific membrane antigen monoclonal antibody Ed-5(125I-Ed-5) and normal mice IgG in nude mice bearing human prostate cancer, and to explore the feasibility for diagnosis of radioimmunoimaging and clinical use of radiation therapy with 125I-Ed-5 to treat human prostate cancer. Methods: The nude mouse xenografted models with human prostate cancer were established. Anti-human PSMA monoclonal antibody Ed-5 and NMIgG was labeled with 125I. 0.526MBq labeled antibody was injected through tail vein of nude mice xneografted with human prostate cancer. Radioactivity ratio of tumor and non-tumor (T/NT), percent injected dosage of every gram tissue (%ID/g) were measured after 24, 48, 72, 120 hours interval of injection, and the biodistribution of labeled antibody were studied. Results: The labelling rate of 125I-Ed-5 was 72.3%, the specific activity of 125I-Ed-5 was 55.2MBq/mg, the radiochemical purity of 125I-Ed-5 was 90.2%, and the inmmunoreactive fraction was 63%. Radioactivity concentration of tumor was found during the 24-120 hours after the 125I-Ed-5 injection. The peak time of 125I-Ed-5 concentration in the xenograft was about 72 hour after injection when the radioactivity ratios between tumor and various tissues were the highest. The highest T/NT radioactivity ratio of tumor/muscle was 6.36. But non-concentration of 125I-NMIgG was found, which was distributed evenly in body. Conclusions: The immune activity of the 125I-Ed-5 does not change. The results indicated that 125I-Ed-5 can be located to xenografted human prostate cancer, and it might be used for the imaging and the targeting treatment of prostate cancer.