Tumor uptake of intravenously administered radiolabeled antibodies in ovarian carcinoma patients in relation to antigen expression and other tumor characteristics

Abstract

To study factors that possibly influence the heterogeneous tumor uptake of radiolabeled antibodies, tissues from 34 ovarian-carcinoma patients were obtained 2 to 8 days after i.v. injection with radiolabeled murine OV-TL3 or chimeric MOv18 (cMOv18). The tumor uptake and the ratio of tumor to normal tissue (T/NT) were studied in relation to the histopathological classification, prior treatment, site of tumor, time interval, antigen expression, volume percentage of (malignant) epithelium in the tumor tissue, and the size of the tumor. The results of immunoscintigraphy were also included. In addition, autoradiography using storage phosphor technology was performed on tissue sections from patients injected with iodine-labeled cMOv18. Tumor uptake varied largely, not only between patients, but also between tumor deposits within the same patient. Uptake of OV-TL3 F(ab')2 was higher than of cMOv18 F(ab')2, but the T/NT ratios were similar. The antibody uptake was positively correlated with the pattern of antigen expression and inversely correlated with the time interval between injection and surgery. No correlation was observed with any of the other factors studied. The visibility with immunoscintigraphy was related to the size of the detected lesion, but not to the other factors studied. Autoradiography showed that antibodies preferentially localized in areas with cancer cells, which were immunohistochemically positive for MOv18. In areas with weak antigen expression, autoradiography revealed less activity. The antigen expression by the tumor is an important factor for estimation of the tumor uptake of radiolabeled antibodies.

HPMA copolymer–anticancer drug–OV-TL16 antibody conjugates. II. Processing in epithelial ovarian carcinoma cells in vitro

“…In a study of ovarian carcinoma patients, no correlation was observed between uptake of radiolabeled Abs and tumor size. In addition, only 2 of the 7 tumors tested showed that uptake in the periphery of the tumors was higher than in the center (Buist et al, 1995a). Our results in combination with the above-mentioned attributes support the potential usefulness of the OV-TL16 Ab as a targeting moiety.…”

“…However, in certain malignancies, this approach may prove to be effective. For instance, the ovarian cancer-specific Ab OV-TL3, sharing the same antigen (OA3) with the OV-TL16 Ab (used in this study), is distributed homogeneously in solid ovarian tumors (Buist et al, 1995a). Therefore, for this type of cancer it may be expected that an Ab-targeted cytotoxic conjugate could accumulate uniformly within the solid tumor tissue.…”

Immunohistochemical analysis of intratumoral heterogeneity of [131I]cG250 antibody uptake in primary renal cell carcinomas

“…and the few results of clinical studies are contradictory: Buist et al (1995) investigated the relation between a number of tumour characteristics and uptake of the MAbs OV-TL 3 and chimeric MOv 18 in tumour samples of patients with ovarian carcinoma. A close correlation between antibody uptake and antigen expression was shown.…”

Selection of monoclonal antibody E48 IgG or U36 IgG for adjuvant radioimmunotherapy in head and neck cancer patients

“…It is not yet clear which patient and tumour characteristics influence tumour uptake of MAbs. Buist et al (1995b) analysed several tumour characteristics in ovarian cancer patients. Only antigen expression was proved to be related to tumour uptake.…”