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Tumor Detection with ¹³¹I-labeled Human Monoclonal antibody COU-1 in Patients with Suspected Colorectal Carcinoma¹

Department of Medical Microbiology, Odense University, Winslowparken 19, [H. D, K. E.], and Departments of Nuclear Medicine [J. W. R., E. L.], Surgery [P. B-C., I. T, O. K.], and Pathology [C. F.], Odense University Hospital, 5000 Odense, and Institute of Medical Microbiology, Aarhus University, 8000 Aarhus [J. C. J], Denmark

A major factor limiting the use of rodent monoclonal antibodies for diagnosis and therapy of cancer is the development of human anti-mouse immunoglobulin antibodies. Here we report a phase I/II immunodetection study of a human monoclonal antibody, COU-1, labeled with ¹³¹I. COU-1 is produced by a human-human hybridoma and recognizes a M_r 43,000 cytokeratin-like protein strongly expressed by adenocarcinomas of the colon, breast, and ovary. Ten patients were given an i.v. infusion of 2 mg of antibody COU-1 labeled with 185 MBq of ¹³¹I. No adverse effects or toxicity were detected by conventional clinical tests nor by a complement activation assay for C3d. None of the patients developed antibodies against antibody COU-1 as determined by enzyme-linked immunosorbent assay and agglutination analysis. Tumor detection was successful in 7 of 9 cancer patients. The tenth patient proved to be a true negative. In several instances immunoscintigraphy gave additional or more correct information than conventional detection techniques. Tumors were most clearly outlined at days 5 and 7 after infusion. Primary colorectal carcinomas were detected by planar imaging in the cecum, ascending colon, and rectum with the smallest lesion measuring 3.0 cm in diameter. Immunoscintigraphy revealed multiple liver metastases in 1 of 3 patients. However, the livers of all 3 patients contained significantly more radioactivity (P < 0.005) than tumor-free livers of the other patients. Pharmacokinetics was evaluated in all patients. The clearance of ¹³¹I-labeled COU-1 from the circulation followed a triphasic pattern; an initial phase [t = 0.4 ± 0.4 (SD) h] cleared 23% of the radioactivity followed by a rapid phase with a half-life of 13 ± 3.8 h. The third phase (ß-phase) exhibited a half-life of 119 ± 36 h, which is similar to the half-life reported for normal IgM. The human monoclonal antibody COU-1 directed against a predominantly intracellular cancer-associated antigen does not produce toxicity or induce antibody formation and seems to be a promising agent for detecting tumors with immunoscintigraphy.

¹ The study was supported by the Danish Pharmaceutical Company, GEA, Ltd.

² To whom requests for reprints should be addressed at, Department of Immunology (IMM2), The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037.

Received 5/21/93. Accepted 10/ 9/93.

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