Regino C A S, Wong K J, Milenic D E, Holmes E H, Garmestani K, Choyke P L, Brechbiel M W
Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1088.
Curr Radiopharm. 2009 Jan;2(1):9-17. doi: 10.2174/1874471010902010009.
Better tumor markers are needed for early diagnosis and staging of prostate cancer, and for monitoring therapeutic response than the currently used prostate specific antigen (PSA). Prostate specific membrane antigen (PSMA) is highly expressed on the surface of prostatic epithelial cells making it a good target for prostate cancer. In this study, mAb 3C6, specific for the extracellular epitope of PSMA, was evaluated both in vitro and in vivo for PSMA-targeting. Immunoreactivity and specificity of mAb 3C6 was evaluated by flow cytometry using prostate cell lines expressing PSMA such as LNCaP and 22Rv1 and a cell line, DU145, that expresses very little PSMA. 3C6 was conjugated with the acyclic CHX-A" DTPA chelate, radiolabeled with (111)In, and its in vitro and in vivo properties were assessed. The biodistribution of the radioimmunoconjugate evaluated in athymic mice bearing xenografts of three human prostate carcinoma cell lines shows high uptake after 72 hr in LNCaP tumors (%ID/g 22.93 +/- 6.32) and 22Rv1 (%ID/g 10.44 +/- 2.32) in contrast to low uptake by the DU145 tumors (%ID/g 4.27 +/- 0.37). Planar gamma-scintigraphic images obtained for xenografted tumor bearing mice demonstrated targeting for PSMA positive tumors suggesting possible applications in imaging and for targeted radiation therapy.
与目前使用的前列腺特异性抗原（PSA）相比，前列腺癌的早期诊断、分期以及监测治疗反应需要更好的肿瘤标志物。前列腺特异性膜抗原（PSMA）在前列腺上皮细胞表面高度表达，使其成为前列腺癌的一个良好靶点。在本研究中，针对PSMA细胞外表位的单克隆抗体3C6在体外和体内进行了PSMA靶向评估。使用表达PSMA的前列腺细胞系（如LNCaP和22Rv1）以及表达极少PSMA的细胞系DU145，通过流式细胞术评估单克隆抗体3C6的免疫反应性和特异性。3C6与无环CHX-A”DTPA螯合物偶联，用（111）In进行放射性标记，并评估其体外和体内特性。在携带三种人前列腺癌细胞系异种移植瘤的无胸腺小鼠中评估放射性免疫偶联物的生物分布，结果显示72小时后，LNCaP肿瘤（%ID/g 22.93±6.32）和22Rv1肿瘤（%ID/g 10.44±2.32）摄取较高，而DU145肿瘤摄取较低（%ID/g 4.27±0.37）。对携带异种移植瘤小鼠获得的平面γ闪烁图像显示，PSMA阳性肿瘤有靶向性，提示其在成像和靶向放射治疗中可能有应用。
