The overall goal of Project #5 has changed since the previous application. During the first two years of funding, hepatobiliary paramagnetic agents were targeted to liver cells, and their efficacy was assessed by MR imaging. In the last year of funding, efforts have concentrated on the development of a new class of MR contrast agents for receptor and antigen imaging. These agents consist of monocrystalline iron oxide nanoparticles (MION) that can be readily attached to a variety of carrier molecules, delivered to receptor sites in vivo, and detected by MR imaging. The scope of the proposed research includes the physical and biochemical characterization of both the parent particles (MION) that are targeted to hepatic (e.g., asialoglycoprotein receptor) and pancreatic cells (e.g., secretin receptor). The small size of MION (2.9 + 0.0nm), which facilitates transcapillary passage, results in a relatively low relativity in vitro. A more dramatic effect, however, is observed in vivo. A component of this study will investigate the mechanism of action of these agents. The preclinical utility of unlabeled and labeled MION will be assessed in vivo in animal models and in vitro in studies of benign and malignant human tissue. The long term goals of this research are to:a) improve the detection of cancer, and b) allow determination of organ function in vivo.
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