Radioimmunoguided surgery in colorectal cancer using a genetically engineered anti-CEA single-chain Fv antibody

In radioimmunoguided surgery (RTGS), a radiolabeled antibody is given i.v. before surgery and a hand-held gamma-detecting probe is used to locate tumo r in the operative field. The rapid blood clearance and good tumor penetrat ion of single-chain Fv antibodies (scFv) offer potential advantages over la rger antibody molecules used previously for RIGS. A Phase I clinical trial is reported on RIGS with scFv (MFE-23-his) to carcinoembryonic antigen (CEA ). Thirty-four patients undergoing surgery for colorectal carcinoma (17 pri mary tumors, 16 liver metastases, and 1 anastomotic recurrence) and 1 patie nt with liver metastases of pancreatic carcinoma received I-125-labeled MFE -23-his scFv (I-125-MFE-23-his) 24, 48, 72, or 96 h before operation. I-125 -MFE-23-his showed biexponential blood clearance with alpha and beta half-l ives of 0.32 and 10.95 h, respectively. The abdomen was scanned during surg ery with a hand-held gamma detecting probe (Neoprobe Corp.). I-125-MFE-23-h is showed good tumor localization; comparison with histology showed overall accuracy of 84%, Highest median ratios for tumor:normal tissue and tumor:b lood were recorded 72 or 96 h after scFv injection for patients undergoing resection of liver metastases, High levels of radioactivity were found in t he kidneys, Five patients had grade 1 fever, and three had a grade 1 rise i n blood pressure according to the Common Toxicity Criteria. There was a sig nificant correlation between these ratios and those measured in excised tis sues using a laboratory gamma counter (P < 0.001). MFE-23-his scFv antibody localizes in CEA-producing carcinomas. The short interval between injectio n and operation, the lack of significant toxicity, and the relatively simpl e production in bacteria make MFE-23-his scFv suitable for RIGS.