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Relationship of Radioantibody Localization and Cell Viability in a Xenografted Human Cancer Model as Measured by Whole-Body Autoradiography¹

Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103

The simultaneous distribution of monoclonal ¹³¹I-labeled anti-carcinoembryonic antigen (CEA) immunoglobulin (IgG) (NP-2) or ¹³¹I-labeled irrelevant myeloma IgG (Ag8) and [³H]thymidine was studied in hamsters bearing transplants of the GW-39 human colon carcinoma by qualitative double-tracer whole-body autoradiography. Autoradiography showed that large solid GW-39 tumors are characterized by heterogeneity of radioantibody retention and uneven [³H]thymidine accumulation, reflecting zonal variations in antibody reactivity and tumor cell proliferation, respectively. The autoradiographic images showed that both ¹³¹I-labeled-monoclonal antibody and control ¹³¹I-labeled IgG targeted nonproliferating tumor zones, suggesting a mechanism of nonspecific tumor uptake of radioantibodies in these areas. Absence of tumor center labeling with [³H]thymidine, associated with cellular necrosis, was confirmed by histology and microautoradiography in separate animal studies. In confirmation of earlier reports, ¹³¹I-labeled anti-CEA monoclonal antibody gave higher tumor-to-non-tumor labeling patterns than did control ¹³¹I-labeled IgG, at both 3 and 7 days following treatment. Immunohistochemical localization of CEA in GW-39 tumors with necrotic centers showed the presence of CEA in nonviable cells, but CEA antigen concentrations were diminished as compared to cells located in the tumor's periphery. The results indicate that double-tracer whole-body autoradiography is well suited for studying the kinetics of radioantibody localization in relation to regional tumor cell viability.

¹ Supported in part by NIH Grants CA 37849 and CA 39841. Presented in part at the 77th Annual Meeting of the American Association of Cancer Research.

² To whom requests for reprints should be addressed, at the Center for Molecular Medicine and Immunology, 1 Bruce Street, Newark, NJ 07103.

Received 8/25/86. Revised 12/ 1/86. Accepted 1/16/87.