Radioimmunoguided Surgery in Colorectal Cancer Using a Genetically Engineered Anti-CEA Single-Chain Fv Antibody

• Published in: Clinical cancer research 2000-05, Vol.6 (5), p.1711
• Main Authors: Mayer, A, Tsiompanou, E, O'Malley, D, Boxer, G M, Bhatia, J, Flynn, A A, Chester, K A, Davidson, B R, Lewis, A A, Winslet, M C, Dhillon, A P, Hilson, A J, Begent, R H
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies - genetics; Antibodies - therapeutic use; Carcinoembryonic Antigen - immunology; Colon - drug effects; Colon - metabolism; Colon - pathology; Colorectal Neoplasms - diagnostic imaging; Colorectal Neoplasms - pathology; Colorectal Neoplasms - surgery; DNA, Recombinant - pharmacokinetics; DNA, Recombinant - therapeutic use; Female; Genetic Engineering; Humans; Immunoglobulin Fragments - genetics; Immunoglobulin Fragments - therapeutic use; Iodine Radioisotopes - pharmacokinetics; Liver Neoplasms - diagnostic imaging; Liver Neoplasms - secondary; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphatic Metastasis; Male; Middle Aged; Radioimmunodetection - methods; Tissue Distribution
• ISSN: 1078-0432; 1557-3265

In radioimmunoguided surgery (RIGS), a radiolabeled antibody is given i.v. before surgery and a hand-held gamma-detecting probe is used to locate tumor in the operative field. The rapid blood clearance and good tumor penetration of single-chain Fv antibodies (scFv) offer potential advantages over larger 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 primary tumors, 16 liver metastases, and 1 anastomotic recurrence) and 1 patient with liver metastases of pancreatic carcinoma received 125 I-labeled MFE-23-his scFv ( 125 I-MFE-23-his) 24, 48, 72, or 96 h before operation. 125 I-MFE-23-his showed biexponential blood clearance with α and β half-lives of 0.32 and 10.95 h, respectively. The abdomen was scanned during surgery with a hand-held gamma detecting probe (Neoprobe Corp.). 125 I-MFE-23-his showed good tumor localization; comparison with histology showed overall accuracy of 84%. Highest median ratios for tumor:normal tissue and tumor:blood were recorded 72 or 96 h after scFv injection for patients undergoing resection of liver metastases. High levels of radioactivity were found in the kidneys. Five patients had grade 1 fever, and three had a grade 1 rise in blood pressure according to the Common Toxicity Criteria. There was a significant correlation between these ratios and those measured in excised tissues using a laboratory gamma counter ( P < 0.001). MFE-23-his scFv antibody localizes in CEA-producing carcinomas. The short interval between injection and operation, the lack of significant toxicity, and the relatively simple production in bacteria make MFE-23-his scFv suitable for RIGS.