Relationship of radioantibody localization and cell viability in a xenografted human cancer model as measured by whole-body autoradiography.

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.