The concept of tumor targeting with antibodies for diagnosis and therapy has the potential to revolutionize the management of solid tumors. The overall objective of this program is to design, prepare, and test radiolabeled monoclonal antibodies (MAB) directed against CEA for the imaging of colorectal cancer and to set the stage for the use of labeled antibody for treatment of colorectal cancer.
The aim of this specific project is to take the labeled antibody preparations provided by the CEA-monoclonal antibody-protein chemistry projects and test them in the nude mouse model. The best preparations as determined in the nude mouse model, will be examine in man. The antibodies provided will consist of MAB of mouse and human origin directed against the epitope of CEA identified by the T84.66 MAB. Whole modified and recombinant (engineered) antibodies will be generated to minimize the 2 major problems with radioimmune preparations to date: normal tissue uptake (especially liver) and human immune response to a foreign protein. The animal studies will document tumor imaging and examine mechanisms involved in tissue uptake of In-III labeled antibody in nude mice bearing human colon carcinoma xenografts. The animal studies will examine the effect of various biological parameters of the tumor, host, antibody and isotope on the labeled antibody biodistribution. The nude model will also be used to examine Y-90 and other metal antibody complexes for tumor therapy. Human imaging studies of patients with advanced colorectal cancer will be used to screen for the most effective preparations. From the computer derived imaging, data, algorithms will be developed to estimate tissue biodistribution and dosimetry. Human imaging studies of colorectal cancer patients prior to surgical exploration (R01-CA 42329-02) will provide a correlation between imaging data and actual tissue biodistribution. The ground work for the initiation of human therapy studies using Y- 90 will be laid by the animal (In-III, Y-90) and human (In-III) studies undertaken in this project. The techniques used in evaluating tumor imaging and therapy in the nude mouse and tumor imaging in humans are established and published.
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