The overall goal of this research is to optimize the detection of lymph node metastases, using novel intravenous magnetic resonance (MR) contrast agents. The clinical importance of this project is most relevant in cancer staging. Although conventional non-contrast MR imaging has significant advantages over other imaging modalities, it is still relatively poor in differentiating lymph node metastases from normal lymph nodes and inflammatory or hyperplastic nodes. We have previously developed T2 (monocrystalline iron oxide nanocolloids, MION) and T1 (dextran grafted polymers) MR contrast agents which exhibit high accumulation (> 40% of injected dose per g tissue) in lymph nodes after intravenous administration. One aspect of this research will investigate the mechanism by which lymph node accumulation occurs and how these unique agents escape rapid uptake by liver and spleen macrophages. To achieve homogeneous distribution of magnetic label in lymph nodes, T1 and T2 labels will also be coupled to antibodies directed against leukocyte homing molecules (adressins) on high endothelial venules using previously developed techniques in our laboratory for MR antibody imaging. This research will also investigate the comparative advantages of T1 and T2 lymph node agents in MR imaging studies in normal rodents and in models of inflammatory, hyperplastic and metastatic nodes. MR data will be assessed for absolute change in signal-to-noise, tumor-lymph node contrast-to-noise and diagnostic sensitivity and specificity using histopathological correlates. The long term goals of this research is to develop useful intravenous MR lymph node contrast agents to improve staging and treatment in patients with cancer.
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