FLOURINE-LABELED ANTIBODIES FOR NMR IMAGING OF TUMORS

The purpose of this program is to investigate the application of tumor-specific monoclonal antibodies to detection of cancer by means of nuclear magnetic resonance (NMR) imaging. NMR imaging provides a means of obtaining high-resolution pictures of internal structures without subjecting a patient to large doses of X-rays or radio-active isotope required for other imaging methods. The technique to be developed in this program involves attachment of large numbers of luorine-19 atoms to molecules of a monoclonal antibody which is specific for an antigen on the cell surface of human melanoma. Fluorine-19 has a strong NMR response and is naturally absent from all body fluids and structures except teeth. The fluorine-labeled antibody will be injected into test animals (immunodeficient mice) carrying implanted human melanoma and the distribution of the reagent in the tumor and organs will be determined. In principle, the reagent will be taken up preferentially by the tumor and the resulting concentration of fluorine in the tumor should permit imaging by NMR. Obtaining high resolution by this method depends upon introducing large amounts of fluorine into the monoclonal antibody and retaining the physical properties and immunological specificity of the antibody. This will be accomplished by preparing a water-soluble polymer containing a large amount of fluorine and coupling covalently a small number of polymer molecules to each antibody molecule (or antibody fragment) in a way that avoids blocking the combining sites. Because antibodies have similar structures, regardless of their specificity, the methods developed in this program should be applicable to antibodies directed against any tumor or immunologically distinct tissue.