A New Magnetic Resonance Imaging Contrast Agent for the Detection of Glutathione

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Guinn, Amy Rebecca
Murthy, Niren
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Magnetic resonance imaging (MRI) is one of the most powerful imaging techniques for research and clinical diagnosis. To expand upon the intrinsic capabilities of MRI, new contrast agents that can detect the presence of biomarkers in vivo are being developed. My Masters thesis research focuses on the design and synthesis of a new MRI contrast agent that can detect glutathione (GSH), a biomarker that has been implicated in a number of oxidative stress diseases. This new MRI contrast agent is based on chelated dysprosium (Dy), an inorganic metal, which provides negative contrast to surrounding tissue. Preliminary data has shown that attaching a poly(ethylene glycol) (PEG) chain to the Dy chelate, effectively increasing its molecular weight, enhances the contrast ability of Dy. Using this new information, the contrast agent was designed to have a large molecular weight PEG chain attached to the Dy chelate through a disulfide, creating a thiol-sensitive linkage. In the presence of a thiol-containing molecule such as GSH, the Dy will be dePEGylated through a disulfide exchange reaction, removing the molecular weight effect of the PEG, and allowing for the detection of GSH by MRI. This new MRI contrast agent could provide insight into the progression and diagnosis of oxidative stress pathologies associated with GSH.
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