Distribution of radiolabelled anti‐CA125 monoclonal antibody OC125‐F(ab′)2‐fragment following resection guided by antibodies (REGAJ) in ovarian cancer patients

Abstract

Ovarian cancer is a highly malignant tumor of mainly postmenopausal women. The long-term prognosis of this malignancy is largely determined by micrometastasis present at the time of second-look surgery. In general, patients face a poor outcome. New radio-immunoscintigraphic methods to target tumor tissue specifically via antigen-antibody binding were developed. However, few studies so far investigated the pattern of in vivo distribution of radiolabelled mAbs and/ or the specificity of antigen-antibody interaction. In this study we examined the immunological interaction and distribution of 131l-OC125-F(ab')2-fragment, an anti-CA-125 mAb, in patients with CA-125 positive ovarian malignancies. Sixteen patients with primarily CA-125 positive gynecological tumors underwent REGAJ surgery. Biopsies of tumor tissue and not tumor infiltrated tissue, serum, and ascites were sampled during or prior to REGAJ surgery, respectively. After preparation of tissue cytosols, samples were assessed for CA-125 and radioactive uptake. By radiochromatography immunological analysis for presence of the target antigen CA-125, the mAb 131l-OC125-F(ab')2-fragment, and immune complexes was performed on different specimen. CA-125 concentrations were higher in serum samples, ascites, and malignant tissue biopsies of malignoma patients compared to those without signs of malignant disease. CA-125 was higher in the tissue cytosol than in the cell membrane fraction. Gel filtration revealed CA-125 with moieties of 75,000 to > 600,000 d. Accumulation of radioactivity was more frequently associated with the presence of unbound 131l-OC125-F(ab')2-fragment or high molecular weight immune complexes. Radioactive uptake, however, was not confined to tissue of high CA-125 expression. Moreover, both immune complex as well as 131l-OC125-F(ab')2-fragment could be isolated from cytosols of tissue not infiltrated by tumor cells as well. Our study demonstrates that the majority of CA-125 is located intracellularly and thus inaccessible to 131l-OC125-F(ab')2-fragment per se. The uptake of 131l-OC125-F(ab')2-fragment into the cytosol of tumor-free and malignant tissue samples prompts us to speculate that certain mechanisms for antigen-specific and nonspecific cellular trafficking of mAbs do exist. We present a model to explain our observations.