Methods in Oxygen Imaging Applied to Cancer Systems and Cancer Modulating Therapies

Grace Abigail Murley, BA, BS (Advisor: Clifton Fuller, MD, PhD)

     Hypoxia, or low tissue oxygenation, is a frequently observed phenomenon in cancer. It is associated with poor prognosis due to multiple mechanisms. Hypoxia results in increased rate of metastasis, resistance to apoptosis, and decreased efficacy of therapeutics such as chemotherapy, immunotherapy, and radiation therapy. Overall, proper assessment of hypoxic status of tumors permits improved patient diagnosis and tailored treatment planning. More novel in vivo metrics have gained prominence and could allow for tumor assessment without the need for tumor biopsy. Electron paramagnetic resonance imaging (EPRI), multispectral optoacoustic tomography (MSOT), and positron emission tomography (PET) performed with [¹⁸F]-fluoroazomycin-arabinoside ([¹⁸F]-FAZA) are able to assess hypoxia in vivo. EPRI can be used to measure oxygenation under different breathing gas conditions which can be correlated with gastric crypt sparing after FLASH radiotherapy. MSOT can be used on inguinal lymph nodes suspicious for metastasis to differentiate between reactive lymph nodes and those with true metastases. [¹⁸F]-FAZA PET, compared with EPRI, is a superior imaging methodology for assessing improvement in oxygenation after complex I inhibition with rotenone. Lastly, EPRI can be used to measure oxygenation changes after the allosteric hemoglobin inhibitor, myo-inositol trispyrophosphate (ITPP), is administered. Overall, this work shows how these techniques can be used for improved lymph node stratification, prediction of patient response to radiation, and assessment of oxygenation changes after administration of adjuvant therapies. This all has the potential to accelerate patient care and improve tailored treatment strategies leading to better outcomes.

Advisory Committee:

• Clifton Fuller, MD, PhD, Chair
• Pratip Bhattacharya, PhD
• Mary Farach-Carson, PhD
• Mark Pagel, PhD
• Wendy Woodward, MD, PhD

Join via Zoom (Please contact Ms. Murley for her Zoom meeting info.)