NMR RECEPTOR IMAGING

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The goal of this research is to extend our previous magnetic resonance (MR) receptor imaging research and develop novel immunospecific contrast agents for the in vivo characterization of cancer. These agents ideally act as ~molecular probes~ for cell surface structures either in normal tissue or in tumor tissue. During the previous funding period, we have successfully synthesized and directed superparamagnetic magnetoconjugates to asialoglycoprotein receptors on hepatocytes and to cholecystokinin (CCK) receptors on pancreas cells and demonstrated improved differentiation of benign and malignant lesions (MR receptor imaging). In the current Project we propose to a) complete the investigations of MR receptor imaging of the pancreas and b) to extend previous research to antigenic and/or receptor sites present on malignant cells. We present data on magnetoimmunoconjugates based on a monocrystalline iron oxide nanocompound (MION) including studies to optimized our coupling strategies and showed that most of the antibody affinity can be retained through conjugation. The proposed research expands on successful in vivo cell culture experiments and in vivo MR imaging with such antibody MION conjugates directed to tumor cell surface structures (MION-L6) or internalized compartments (MION-BR96). We anticipate that results, models and conjugation technology from this research can be used to assess cell surface structure in a variety of neoplastic systems (breast cancer, lung cancer, pelvic malignancies, lymphoma etc.) MR imaging of tumor antigens is expected to allow in vivo typing of malignant tissues, to enhance detection of cancer and to predict efficacy of immunotherapy with chemoconjugates and immunotoxins.