Date of Graduation
5-2020
Document Type
Thesis
Degree Name
Bachelor of Science
Degree Level
Undergraduate
Department
Biomedical Engineering
Advisor/Mentor
Muldoon, Timothy J.
Abstract
Despite a plethora of medical advancements, malignant tumors remain difficult to treat due to complex cancer biology and interpatient heterogeneity. Phenotypically similar tumors may respond differently to a given treatment. In clinical oncology, it is paramount to quantify tumor response to therapy for predicting treatment outcome, monitoring tumor changes, identifying effective therapies, and avoiding unnecessary cost and toxicity to the patient. Current standards of monitoring tumor response to therapy include CT, MRI, PET, and histopathology; these methods either take a merely anatomical approach or are invasive and time consuming, necessitating a functional biomarker approach. MPM represents a metabolic-level method of effectively quantifying tumor response that is noninvasive and achieves high spatial resolution and increased imaging depth. This thesis pursued creation of a benchmark for 5-FU-induced apoptosis in CRC cells based on CC3 frequency in order to use this marker to verify TPEFM as an ex vivo method of quantifying patient-specific CRC tumor response to 5-FU via changes in optical redox ratio as an indicator of apoptosis. Lack of sensitivity of the Western blot protocol to CC3 precluded accurate quantification of CC3 frequency over 5-FU exposure times and concentrations. Significant changes in redox ratio throughout 5-FU exposure times were observed but may remain inconclusive when considering the metabolic properties of most cancers. Although redox ratio imaging was successfully conducted here, redox ratio data was not correlated with a reliable marker of apoptosis in the same context. With further apoptosis assays and more rigorous exploration of the relationship of redox ratio, the metabolic profile of CRC cells, and 5-FU-induced apoptosis in CRC cells, TPEFM may be established as a high-resolution metabolic technique for monitoring treatment effectiveness in this context and with novel drugs and other cancer types.
Keywords
redox ratio; apoptosis; colorectal cancer; 5-fluorouracil; cleaved caspase-3; multiphoton microscopy
Citation
Larey, A. (2020). Optical Metabolic Imaging as a Predictor of Patient Tumor Response to Therapy and Apoptosis. Biomedical Engineering Undergraduate Honors Theses Retrieved from https://scholarworks.uark.edu/bmeguht/93
