Study, Evaluation, and Applications of MRI Contrast Agents that Work Based on CEST and T2-EX Mechanisms

Abstract

MRI is a powerful imaging method that offers several advantages including non-ionizing radiation, significant depth of penetration, and great spatial resolution. Current demand for precision medicine and the movement toward personalized medicine have encouraged researchers in the field of medical imaging to develop MRI-based techniques. Various techniques are now available for molecular imaging by MRI. MRI started by utilizing T1 relaxation properties of molecules but soon after other relaxation mechanisms such as T2 and recently Chemical Exchange Saturation Transfer (CEST) were developed. Each of those MRI techniques offers advantages and disadvantages such as differences in experimental procedures, complexity of the method, selectivity and specificity of signals, and translation into clinical applications. We have been developing MRI techniques and responsive contrast agents for CEST MRI in the Pagel laboratory (Contrast Agent and Molecular Imaging Laboratory, also called CAMEL) for the past decade. We have mainly utilized MRI techniques and responsive contrast agents to detect and measure cancer biomarkers. Detection of the activity of enzymes and measurement of pH have been our main focus, and we have developed catalyCEST MRI probes and techniques for the detection of the activity of enzymes and acidoCEST for the measurement of pH. My research started with investigation on paramagnetic agents as potential CEST MRI probes (paraCEST) and continued with an investigation on diamagnetic agents (diaCEST). I completed several projects in which I prepared and evaluated paraCEST and diaCEST contrast agents for the detection of DT-diaphorase, and alkaline phosphatase enzymes, respectively. Although CEST MRI was my main activity in CAMEL, I started a new direction in CAMEL after encountering a series of observations that were unexplainable with CEST MRI. Through my research, I introduced a new class of responsive contrast agents based on the T2-Exchange (T2-Ex) relaxation mechanism. I employed the T2-Ex mechanism to evaluate responsive contrast agents for the detection of nitric oxide biomolecule and nitroreductase enzyme. My research activities in the CAMEL group resulted in one review paper, one book chapter, two published research articles, and two submitted research manuscripts at the time of preparing my PhD dissertation. In addition to my projects, I was involved in another project that focused on nanocapsule drug delivery, which resulted in a second author publication.