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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042329-02
Application #
3183463
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1986-05-01
Project End
1989-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
City of Hope National Medical Center
Department
Type
DUNS #
City
Duarte
State
CA
Country
United States
Zip Code
91010
Neumaier, M; Gaida, F J; Lewis, M R et al. (1999) A chimeric anti-CEA antibody with heavy interchain disulfide bonds deleted: molecular characterization and biodistributions in normal and tumor bearing mice. Anticancer Res 19:13-21
Hu, S; Shively, L; Raubitschek, A et al. (1996) Minibody: A novel engineered anti-carcinoembryonic antigen antibody fragment (single-chain Fv-CH3) which exhibits rapid, high-level targeting of xenografts. Cancer Res 56:3055-61
Wu, A M; Chen, W; Raubitschek, A et al. (1996) Tumor localization of anti-CEA single-chain Fvs: improved targeting by non-covalent dimers. Immunotechnology 2:21-36
Beatty, J D (1992) Immunotherapy of colorectal cancer. Cancer 70:1425-33
Wilson, L A; Kuhn, J A; Corbisiero, R M et al. (1992) A technical analysis of an intraoperative radiation detection probe. Med Phys 19:1219-23
Price, T; Beatty, B G; Beatty, J D et al. (1991) Human anti-murine antibody interference in measurement of carcinoembryonic antigen assessed with a double-antibody enzyme immunoassay. Clin Chem 37:51-7
Corbisiero, R M; Yamauchi, D M; Williams, L E et al. (1991) Comparison of immunoscintigraphy and computerized tomography in identifying colorectal cancer: individual lesion analysis. Cancer Res 51:5704-11
Morton, B A; O'Connor-Tressel, M; Beatty, B G et al. (1988) Artifactual CEA elevation due to human anti-mouse antibodies. Arch Surg 123:1242-6
Beatty, J D; Duda, R B; Williams, L E et al. (1986) Preoperative imaging of colorectal carcinoma with 111In-labeled anticarcinoembryonic antigen monoclonal antibody. Cancer Res 46:6494-502
Beatty, B G; Paxton, R J; Sheibani, K et al. (1986) Testis imaging with 111In-labeled anticarcinoembryonic antigen monoclonal antibody: identification of carcinoembryonic antigen in normal germ cells. Cancer Res 46:6503-8