Imaging of primary and metastatic colorectal carcinoma with monoclonal antibody 791T/36 and the therapeutic potential of antibody-drug conjugates.
Monoclonal antibody 791T/36, prepared against a tumour-associated 72,000 dalton glycoprotein, reacted with cells from primary and metastatic colorectal carcinomas. I-131 or In-111-labelled antibody localized in xenografts of colorectal carcinomas established from in vitro clonogenic populations. Clinically, with I-131-labelled antibody, 8/11 colonic tumours imaged positively. Imaging was negative in four patients with benign colon disease. 5/11 rectal tumours were positively imaged, but excreted I-131 in the bladder obscured tumours in several studies. In-111-labelled antibody gave superior images and positively imaged primary and metastatic sites in 13/14 patients. Prospectively in the detection of recurrent disease, I-131 or In-111-antibody detected 29/33 separate sites in 24 patients. Seven negative patients remain disease free. There were 3 false positives; overall sensitivity was 88%, with 70% specificity. Specific localization of radiolabel was confirmed immunochemically and by counting radioactivity in resected specimens. Antibody conjugates with methotrexate, vindesine and daunomycin retained drug activity and antibody function, including xenograft localization and conjugates were therapeutically effective against xenografts. 791T/36 antibody has potential for immunodetection of primary and recurrent colorectal carcinoma and for targeting of therapeutic agents.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007205:Indium Radioisotopes; D008727:Methotrexate / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D012004:Rectal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D013934:Thymectomy; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D008727:Methotrexate