The Modulation of Magnetic Properties In Magnetic Resonance Imaging Contrast Agents using Enzymes

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Magnetic resonance imaging (MRI) is an advanced imaging modality that is experiencing increasing popularity in clinical and experimental settings. MRI enjoys the benefit of high-resolution, the use of non-ionizing radiation, and the ability to distinguish between soft tissues. MR imaging is enhanced with the use of Gd3+ chelated contrast agents; however the current commercially available contrast agents for MRI are low relaxivity, monomeric vascular agents. A new generation of MR contrast agents has been developed that addresses the need for these agents to respond to localized biological environments. This thesis expands upon a family of enzyme-activable MR contrast agents. This thesis concerns the design, synthesis, and characterization of lanthanide complexes that change relaxivity in response to hydrolyzing enzymes. Chapter 2 describes a MR contrast agent with a pendant galacto-D-pyranose sugar attached to a Gd3+ chelator via a self-immolative linker that is sensitive to beta-galactosidase. Chapter 3 introduces a phosphatase activatable MR contrast agent that uses an inter- and intra-molecular binding to inhibit inner sphere water molecules from coordination to the lanthanide. Chapter 4 describes the use of an alkyl bridge to block water access to the macrocyclic Gd3+ chelator. The addendum presents a nitrogen mustard alkylating agent conjugated to a Gd3+ chelate to slow the tumbling rate once attached to DNA.

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  • 09/17/2018
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