| Abstract: | The potential of radioiodinated monoclonal antibody B72.3 for lymphoscintigraphy was evaluated, using suitable animal models of a human colorectal carcinoma. LS174T xenografts were grown at various sites in beta-estradiol-pretreated athymic mice, and the development of metastases in different organs was assessed histologically. After iv inoculation of the mice, 66% of the animals developed "metastases" to the axillary lymph nodes. Of these mice, 100% also developed multiple tumors on their backs and 79% had lung micrometastases. Livers, kidneys, and spleens showed no evidence of tumor growth. In 33% of the mice in which primary LS174T tumors had been removed from the hindfoot pad, metastases to the popliteal lymph nodes were observed 3 1/2 weeks after tumor implantation. BALB/c (nu/nu) female mice bearing axillary and popliteal lymph node metastases were used to test the potential of radiolabeled B72.3 antibody (an IgG1) as a lymphoscintigraphic agent. A monoclonal antibody against horseradish peroxidase (also an IgG1), which did not bind LS174T tumor cells in vitro, served as a control. Both normal and tumor-bearing axillary and popliteal lymph nodes imaged up to 6 hours after the sc injection of 20-40 mu Ci of 125I-labeled B72.3 into either the forefoot or hindfoot pads. The localization index (L.I.) (specific/nonspecific antibody in tumor divided by specific/nonspecific antibody in blood) for LS174T tumors in lymph nodes was approximately 1 during the first 6 hours after antibody injection, thus indicating no specific antibody accumulation. Twenty-four hours and later after sc injection, images of nodal metastases (14-477 mg) and specific antibody accumulations were observed. At these times the L.I.'s ranged 1.5-3.5. Tumor-negative nodes did not image at 24 hours after injection of 125I-labeled B72.3. The L.I.'s of the normal nodes and of other tissues from these mice were about 1.0 at 24 hours, indicating no specific antibody accumulation. Autoradiographic analysis of lymph nodes containing LS174T tumor showed heterogeneous antibody distribution of B72.3 within tumor sections with heavy patches of antibody accumulation in mucin globules. In lymph nodes the normal lymphocytes adjacent to the LS174T tumor cells showed no antibody accumulation. The lack of specific, early antibody accumulation by LS174T tumor-bearing nodes in mice suggests that B72.3 does not accumulate in nodal metastases to the degree necessary to consider it a potential agent for use in lymphoscintigraphy. |
