Access Type
Open Access Embargo
Date of Award
January 2023
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Chemistry
First Advisor
Matthew J. Allen
Abstract
This thesis is a collection of seven chapters that discuss the contributions to the field oflanthanide-based contrast agents for magnetic resonance imaging (MRI), particularly in the context of imaging hypoxia and extracellular pH. These physiological changes play a significant role in life-threatening conditions such as cancer, making it essential to develop effective imaging tools to aid in diagnosis and treatment. The thesis provides insights for the rational development of lanthanide-based contrast agents for MRI. A comprehensive review of divalent europium as a tool for imaging hypoxia using magnetic resonance imaging and how coordination chemistry can be used to tune the properties of Eu to enhance contrast in MRI is presented in chapter 2. The chapter discusses how EuII can positively enhance T1-weighted magnetic resonance imaging in the absence of oxygen, but its sensitivity to oxygen poses logistical challenges with respect to administration. The review highlights the use of coordination chemistry to control the inner and outer sphere environments of EuII-containing complexes, enabling effective imaging of hypoxia by tuning electrochemical potentials and relaxivity. The chapter begins with an introduction to magnetic resonance imaging and contrast agents, followed by a description of the coordination chemistry of EuII-containing complexes and their parameters for contrast enhancement. Chapter 3 describes why a new EuII-containing complex that is compatible with systemic delivery is critical for imaging hypoxia. This chapter establishes the need for imaging hypoxia in a noninvasive and direct way to diagnose, stage, and monitor the treatment and development of new therapies for diseases associated with hypoxia. The focus of this chapter is on the potential for Eu-containing contrast agents for in vivo imaging of hypoxia via changes in metal oxidation state from +2 to +3. The chapter describes the screening of a library of ligands that led to the discovery of a complex that persists in oxygenated environments and is capable of persisting in blood long enough for imaging by MRI. On another study related to hypoxia, the correlation between interferon- production and hypoxia via positron emission tomography and MRI using an Eu-based contrast agent is described in Chapter 4. The study uses an oxygen-responsive, europium-containing contrast agent for direct imaging of hypoxia and subsequent interrogation of levels of interferon- via positron emission tomography. The findings suggest that monitoring changes in interferon- levels due to the hypoxic to normoxic switch is critical in the setting of immunotherapy. On another study related to hypoxia, the correlation between interferon- production and hypoxia via positron emission tomography and MRI using an Eu-based contrast agent is described in Chapter 4. The study uses an oxygen-responsive, europium-containing contrast agent for direct imaging of hypoxia and subsequent interrogation of levels of interferon- via positron emission tomography. The findings suggest that monitoring changes in interferon- levels due to the hypoxic to normoxic switch is critical in the setting of immunotherapy. suggests that the new complex has the potential to be a valuable tool for imaging tumor pH in solid tumor cancers. Chapter 6 focuses on the analytical techniques used in Chapters 3, 4, and 5, providing instrumental details and characterization methods, and chapter 7 contains a summary of the thesis and an overview of future research directions. Overall, the thesis presents insights into the development of lanthanide-based contrast agents for MRI and their potential applications in imaging hypoxia and extracellular pH, which could aid in the diagnosis and treatment of various diseases.
Recommended Citation
Rashid, Md Mamunur, "Lanthanide-Based Responsive Contrast Agents For Magnetic Resonance Imaging" (2023). Wayne State University Dissertations. 3875.
https://digitalcommons.wayne.edu/oa_dissertations/3875