Haisma H J, Battaile A, Stradtman E W, Knapp R C, Zurawski V R
Department of Gynecologic Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Int J Cancer. 1987 Dec 15;40(6):758-62. doi: 10.1002/ijc.2910400608.
Monoclonal antibody (MAb) OC125 binds to approximately 80% of epithelial ovarian cancers. Serum antigen, CA125, can be detected in these patients. 131I-OC125-F(ab')2 was injected into 5 ovarian carcinoma patients with preinjection serum levels of 150 to 9,000 CA125 U/ml. Patients received the antibody intravenously in doses ranging from 0.46 to 0.94 mg with a specific activity of approximately 2.5 mCi/mg 131I. The half-life in the circulation was approximately 30 hr and was independent of serum CA125 levels. Clearance of 131I from the circulation fitted an open, one-compartment mathematical model. Gel filtration chromatography revealed antibody-antigen complexes in sera 15 min after injection of the radiolabelled antibody. By 5 days after injection, the free form of OC125 antibody could not be detected in the serum. The rate of complex formation correlated well with the observed preinjection serum CA125 levels. This direct correlation was verified in vitro using purified CA125 antigen and radiolabelled OC125 F(ab')2 fragments. The specific effects of complex formation on tumor localization remains unclear. However, the presence of complexes should not be ignored, when planning for diagnostic imaging or immunotherapy with OC125 or other MAbs reacting with circulating antigen.
单克隆抗体（MAb）OC125可与约80%的上皮性卵巢癌结合。这些患者血清中可检测到抗原CA125。将131I-OC125-F(ab')2注入5例卵巢癌患者体内，注射前血清CA125水平为15至9000 U/ml。患者静脉注射抗体，剂量为0.46至0.94 mg，比活约为2.5 mCi/mg 131I。其在循环中的半衰期约为30小时，且与血清CA125水平无关。131I从循环中的清除符合开放的一室数学模型。凝胶过滤色谱显示，注射放射性标记抗体15分钟后血清中存在抗体-抗原复合物。注射后5天，血清中检测不到游离形式的OC125抗体。复合物形成速率与注射前观察到的血清CA125水平密切相关。使用纯化的CA125抗原和放射性标记的OC125 F(ab')2片段在体外验证了这种直接相关性。复合物形成对肿瘤定位的具体影响尚不清楚。然而，在用OC125或其他与循环抗原反应的单克隆抗体进行诊断成像或免疫治疗时，不应忽视复合物的存在。
