The Modulation of Magnetic Properties In Magnetic Resonance Imaging Contrast Agents using EnzymesPublic Deposited
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.