This study was undertaken to determine the effect of tumor size and tumor carcinoembryonic antigen (CEA) content on the uptake of indium 111 (111In)‐labeled anti‐CEA monoclonal antibody in nude mice bearing xenografts. The tumor cell lines were WiDr, SW403, and LS174T, human colon cancer derivatives. The murine breast carcinoma cell line EMT‐6 was used as a control. Tumor CEA levels (ng/g) of tumor standard error of the mean [SEM], measured by enzyme immunoassay (EIA) were: EMT‐6, 0; WiDr, 105 ± 5.7; LS174T, 2052 ± 198; SW403, 17,575 ± 1,785. The 111In‐labeled monoclonal antibody was injected intravenously into mice bearing a single tumor. At 48 hours postinjection, scintiscan was performed, and the mice were killed so that biodistribution studies could be performed. The uptake of the monoclonal antibody was expressed as percent injected counts per minute per gram of tissue ± SEM. The non‐CEA‐producing tumor, EMT‐6, showed the lowest tumor uptake (1.4 ± 0.3). WiDr, an intermediate CEA‐producing tumor, showed some tumor uptake (16.4 ± 1.5). The high CEA‐producing tumors, SW403 and LS174T, had high tumor uptake (29.5 ± 5.0 and 51.1 ± 6.1, respectively). Biodistribution and scintiscan quality were closely related. Although LS174T had the best tumor uptake, SW403 had the highest CEA tumor content, indicating tumor CEA content cannot entirely predict scintiscan and biodistribution results. Tumor‐to‐blood (T/B), tumor‐to‐liver (T/L), and liver‐to‐blood (L/B) ratios were calculated for each animal and compared with tumor size. It was found that T/L had a negative correlation with tumor size (r = −0.72) and L/B had a positive correlation with tumor size (r = 0.94). These ratios may be useful clinically to follow response to therapy.
Patients with primary and/or metastatic colorectal cancer who had been scheduled for operative intervention were injected intravenously with 200 micrograms of a high-affinity anti-carcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111-indium (Indacea). Patients were imaged by gamma camera at 24 and 48 hours. Primary tumors were identified in 3/10 cases and were not visualized in 3/10 cases. Four scans were considered equivocal. Hepatic metastases were identified as image defects in 5/13 cases and were not visualized in 8/13 cases. All tumors contained CEA by immunoperoxidase staining. In all cases, the primary tumor uptake (5.44 +/- 1.07% ID/kg) was much higher than the uptake of the adjacent fat (0.18 +/- 0.04% ID/kg). There was a direct correlation between tumor CEA content, tumor radioactivity, and the imaging of primary tumor by Indacea. High liver uptake (30.3 +/- 3.0% ID/kg), seen when scanning all patients, was the main limitation of imaging and led to photopenic visualization of hepatic metastases. These results suggest that selection of patients with colorectal carcinoma on the basis of tumor CEA content will lead to improved rates of tumor imaging by Indacea in post-surgical scanning.
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