Chemical and Nanomaterial-Based Injectable Dye Platforms Expanding the Possibilities of Translational Molecular Imaging

Abstract

The continual growth of an aging population has led to a greater incidence of disease and a greater dependence on medical imaging for diagnoses, resulting in a growing clinical need for molecular imaging (MI). MI uses chemical tools to probe or interact with biomarkers of disease and aberrant cellular processes, an area of radiology that has been growing rapidly. MI allows for earlier diagnosis of disease since it identifies changes in biomolecular hallmarks prior to anatomical changes, such as tumors. Commonly used imaging modalities like magnetic resonance imaging (MRI) and intravascular optical coherence tomography (IV-OCT), as well as emerging imaging modalities like magnetic particle imaging (MPI), are in need of chemical innovations to provide MI agents for indications or patient populations that are not currently served but that would significantly benefit from them: kidney disease patients who cannot receive contrast-enhanced MRI, in-stent restenosis and atherosclerosis stratification in IV-OCT, and improvements in cell tracking for cell therapies with MPI. This thesis describes the use of chemical, nanomaterial, and biochemical techniques to develop, characterize, and evaluate new MI chemical solutions for challenges that exist within these imaging modalities in vivo. We have identified and characterized a class of organic radical contrast agent known as verdazyl as a new, metal-free MRI contrast agent that qualitatively and quantitatively evaluates kidney function for a patient population that often cannot receive MRI contrast agents due to safety concerns. We have created a new Au nanostructure that both scatters near-infrared II light and binds molecular markers of inflammation, providing MI to IV-OCT. Finally, we have examined the effect of surface chemistry modulation on anionic superparamagnetic iron oxide nanoparticles towards more biomimetic, zwitterionic groups for improving cell uptake for cell tracking purposes. The chemical probes presented in this thesis will be fundamental to pursuing both pre-clinical and clinical solutions to problems in the field of MI.