Dinitroxides in Rapid Scan Electron Paramagnetic Resonance Imaging

<p>Local tissue physiology is an important parameter in understanding disease behavior. Rapid Scan (RS) electron paramagnetic resonance (EPR) offers a unique, non-invasive tool for investigation of these so-called microenvironments through EPR Imaging (EPRI). Research into advancement of EPRI falls into many categories. Not least among those are advances in instrumentation and methodology. Presented here are updates to a benchtop EPRI instrument operating at 1 GHz targeted at pre-clinical EPRI applications. Newly developed methods for reducing RS-EPR background through inversion of the magnetic field are also demonstrated. EPR applications are limited in native biological systems due to the miniscule concentration of paramagnetic species. Because of this, biological EPR and EPRI heavily rely on the use of introduced paramagnetic compounds termed, “probes.” These probes are often organic free-radicals such as triarylmethyl (Trityl) radicals or nitroxides. Attention is given here to an example of a nitroxide that has been structured to provide longer intercellular retention time. In addition to the use of nitroxides as probes, they can also be utilized as nuclear magnetic resonance imaging (MRI) contrast agents via the Overhauser dynamic nuclear polarization (DNP) effects they exert on water protons. A novel employment of this is shown here as an organic radical contrast agent (ORCA). In addition to providing a signal for EPRI to measure, probes can be tuned to provide information about the local cellular environment. Many schemes are employed to utilize this ability of nitroxides (and other radicals) to relay microenvironment information in a spectrum. One such scheme is presented here that utilizes the reversible dissociation of a disulfide bond to detect the glutathione (GSH) mediated cellular redox environment.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Year dc:date.available

2023

Author dc:creator

• Woodcock, Lukas B.

Contributors dc:contributor

• Sandra S. Eaton
• Mark Siemens
• Allegra Aron
• Scott Horowitz
• Brian Michel
• Brian Majestic

• Rapid scan electron paramagnetic resonance (RS-EPR)
• Imaging
• Probes
• Nitroxides
• Organic radical contrast agent (ORCA)
• Chemistry
• Other Chemistry
• Physical Chemistry
• Physical Sciences and Mathematics

Statement dc:rights

• <p>Copyright is held by the author. User is responsible for all copyright compliance.</p>

Language dc:language

English (eng)

Repository record dc:identifier

https://digitalcommons.du.edu/etd/2331

OAI identifier oai:identifier

oai:digitalcommons.du.edu:etd-3321