Clinical application of radioimmunoguided surgery in colorectal cancer using¹²⁵i-labeled carcinoembryonic antigen-specific monoclonal antibody submucosally

Purpose

The aim of this study was to evaluate the applicability of¹²⁵ I-labeled carcinoembryonic antigen-specific monoclonal antibody CL58 in clinical radioimmunoguided surgery for colorectal cancer. METHODS: First, we tested the purity and affinity constant of CL58 and measured the binding affinity of CL58 to colorectal cancer cells and normal cells. Second, we injected¹²⁵I-labeled CL58 into nude mice with colon cancers. Then, samples from the tumor, blood, and normal tissues of injected mice were weighed and counted in a gamma-ray counter for assessment of biodistribution. Finally, we administered¹²⁵Habeled CL58 submucosally in 29 patients with colorectal cancer via endoscope. Radioimmunoguided surgery was performed 3 to 14 days later with a portable gamma-detecting probe to obtain the counts in the target sites. Tumor-to-normal tissue ratio of 3 was taken as the lowest positive threshold value for primary lesions, wall infiltration, and lymph node metastasis. In addition, all the samples were examined by routine histopathology. Lymph nodes negative by routine histopathology were subjected to immunohistochemical staining with anticytokeratin to detect the lymphatic micrometastasis. RESULTS: The affinity constant of CL58 was 7.5 X 10¹⁰ M^-. Moreover, CL58 reacted strongly to the colorectal cancer cell lines, but not to the normal control cells. Furthermore, the tumor tissues showed significant intake of¹²⁵I-labeled CL58, as compared with that of normal tissues. The sensitivity of radioimmunoguided surgery in detecting primary lesions was 93-1 percent, and the specificity of radioimmunoguided surgery to correctly identify negative incisional margins for tumor infiltration was 95.5 percent. For the detection of lymphatic metastasis, the sensitivity of radioimmunoguided surgery was 92.0 percent and the specificity was 87.8 percent. The sensitivity of radioimmunoguided surgery in detecting lymph node metastasis was significantly higher when compared with traditional clinical methods (P = 0.0087). The specificity of radioimmunogu-Supported by a research grant from the National “863” project of China (No. 2001AA215371).