DISTRIBUTION OF RADIOLABELED ANTI-CA125 MONOCLONAL-ANTIBODY OC125-F(AB')(2)-FRAGMENT FOLLOWING RESECTION GUIDED BY ANTIBODIES (REGAJ) IN OVARIAN-CANCER PATIENTS

Ovarian cancer is a highly malignant tumor of mainly postmenopausal wo men. The long-term prognosis of this malignancy is largely determined by micrometastasis present at the time of second-look surgery. In gene ral, patients face a poor outcome. New radio-immunoscintigraphic metho ds to target tumor tissue specifically via antigen-antibody binding we re 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 immunologi cal interaction and distribution of I-131-OC125-F(ab')(2)-fragment, an anti-CA-125 mAb, in patients with CA-125 positive ovarian malignancie s. Sixteen patients with primarily CA-125 positive gynecological tumor s underwent REGAJ surgery. Biopsies of tumor tissue and not tumor infi ltrated tissue, serum, and ascites were sampled during or prior to REG AJ surgery, respectively. After preparation of tissue cytosols, sample s were assessed for CA-125 and radioactive uptake. By radiochromatogra phy immunological analysis for presence of the target antigen CA-125, the mAb I-131-OC125-F(ab')(2)-fragment, and immune complexes was perfo rmed 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 high er in the tissue cytosol than in the cell membrane fraction. Gel filtr ation revealed CA-125 with moieties of 75,000 to >600,000 d. Accumulat ion of radioactivity was more frequently associated with the presence of unbound I-131-OC125-F(ab')(2)-fragment or high molecular weight imm une complexes. Radioactive uptake, however, was not confined to tissue of high CA-125 expression. Moreover, both immune complex as well as I -131-OC125-F(ab')(2)-fragment could be isolated from cytosols of tissu e not infiltrated by tumor cells as well. Our study demonstrates that the majority of CA-125 is located intracellularly and thus inaccessibl e to I-131-OC125-F(ab')(2)-fragment per se. The uptake of I-131-OC125- F(ab ')(2)-fragment into the cytosol of tumor-free and malignant tissu e samples prompts us to speculate that certain mechanisms for antigen- specific and nonspecific cellular trafficking of mAbs do exist. We pre sent a model to explain our observations, J. Clin. Lab, Anal. 11:94-10 3. (C) 1997 Wiley-Liss, Inc.