摘要
目的研究99Tcm-抗前列腺特异性膜抗原(PSMA)抗体(J591)对前列腺癌细胞体外结合性能、在荷人前列腺癌裸鼠体内生物分布。方法用改进的Schwarz方法进行99Tcm标记,经Sephadex G-50柱分离纯化;用纸层析法和三氯醋酸法测定标记率与放化纯;用流式细胞术测定抗体与肿瘤细胞在体外的结合性能;PSMA阳性的C4-2前列腺癌裸鼠为实验组,PSMA阴性的PC3前列腺癌裸鼠为对照组,裸鼠静脉注射7.5 MBq(25μg/只)99Tcm-J591,分别于2、6、12及24h测定体内放射性分布,计算每克组织百分注射剂量率(%ID/g)及T/NT比值。结果表明99Tcm–J591标记率为(78.9±6.2)%,放化纯>90%。J591与99Tcm–J591在体外能结合PSMA阳性的C4-2细胞,与PSMA阴性的PC3细胞不结合,显示出J591具有良好的特异性。生物分布实验显示:实验组裸鼠肿瘤部位出现99Tcm浓聚,对照组则没有。肿瘤组织百分注射剂量率(%ID/g)在12h达高峰,为(15.91±5.16)%ID/g,与对照组(3.22±1.33)%ID/g相比差异有统计学意义(P<0.05),其余组织和器官的百分注射剂量率在两组间差异无统计学意义(P>0.05)。结论 J591具有良好的免疫活性和对前列腺癌的靶向定位性能,可望用于前列腺癌的导向诊断及导向治疗。
Objective To study the binding affinity of 99Tcm labeled anti-human prostatic specific membrane an- tigen （PSMA） monoclonal antibody （McAb） J591 to prostate cancer cells and the biodistribution of 99 Tc ^- J591 in nude mice bearing human prostate cancer. Methods The McAb J591 was labeled with vTcm by improved Schwarz method and the labeled McAb was purified by Sephadex G-50. The binding affinity of J591 with pros- tate cancer cells was measured by Flow Cytometry. The nude mice bearing PSMA-positive C4-2 prostate carci- noma xenografts were served as experiment groups, mice with PSMA-negative pc3 tumors served as controls. The biodistribution of 99Tcm-J591 were carried out in both model nude mice, Results The radiolabeling efficien- cy of 99Tcm-J591 was 78.9 ＋ 6.2%, and radiochemical purity was more than 90% after purification. The 99Tcm-J591 showed a good combination with PSMA-positive C4-2 cells and no combination with PSMA-nega- tive PC3 cells in vitro. The biodistribution results showed that 99Tcm-J591 was accumulated in tumor tissue dur- ing the 2-24 hours after injection in experiment groups, and no significant uptake in control group. The uptake of 99Tcm-J591 in tumor tissue reached a maximum 15.91 ＋5.16 % ID/g in experimental group at 12h post-in- jection. There was a significant difference compared with controls （ P 〈 0.05 ）. There was no significantly difference in other organs uptake between two groups （ P 〉 0.05 ）. Conclusion The monoclonal antibody J591 exhibits an excellent immuno-reactivity and tumor targeting property, and it may be used in diagnosis and target therapy of prostate cancer.
出处
《标记免疫分析与临床》
CAS
2012年第3期160-163,共4页
Labeled Immunoassays and Clinical Medicine
关键词
前列腺癌
前列腺特异性膜抗原
单克隆抗体
生物分布
Prostate cancer
Prostatic specific membrane antigen
Monoclonal antibody Biodistribution
