The objective of this project is to understand the factors that affect the tumor uptake of monoclonal antibidies directed against tumor-associated antigens in humans. By examining tumors for general characteristics, specific antigen properties and uptake of radiolabeled monoclonal antibody; criteria for matching individual tumors with the most appropriate antibody, for radioimmunodetection and/or radioimmunotherapy, will be developed. The anti-CEA monoclonal antibody T84.66.A3.1 will be labeled with In-111 using DTPA to form """"""""Indacea"""""""". Indacea will be used to image patients with cancer who are scheduled for a major operative procedure and/or tumor resection. Assets of this model include: high affinity of the antibody for CEA without crossreactrivity to other CEA-like antigens; retention of full immunological activity by Indacea; stability of In-111 labelling under physiological conditions; decay properties of In-111; renal clearance of unbound In-111 by EDTA chelation instead of separation by column chromatography; and documented tumor-specific imaging of colorectal cancer zenografts in nude mice that correlates with tumor, tumor-associated antigen and In-111 biodistribution characteristics. By comparison of imaging with actual human operative findings, the true specificity and sensitivity of Indacea imaging will be calculated. Human tumor imaging (Indacea imaging) will be compared with resected tissue analysis for tumor size, tumor content and histological distribution of CEA (CEA characteristics), and tumor and normal tissue uptake of In-111 (biodistribution) to identify those factors associated with effective tumor imaging. Subsequent application of these criteria to patients in whom colorectal cancer has previously been resected should allow selection of appropriate candidates for Indacea imaging as part of routine follow-up recurrent disease. The Indacea findings in humans will be compared with those previously documented for human colorectal carcinoma zenografts in nude mice to assess the reliability of this animal mode. In the nude mouse model tumor size correlates with certain biodistribution data. By careful documentation of individual colorectal carcinoma stage and extent of disease at operation, CEA characteristics, and Indacea imaging and biodistribution; the potential value of Indacea for measuring tumor response to treatment will be assessed.
