Doctor of Philosophy (PhD)
Cancer comprises many specific diseases, and it is currently responsible for millions of deaths worldwide. This broad disease profile is a great challenge for personalized oncology. Critical for the success of cancer therapy is the exploration of improved methodologies for the early detection of localized and disseminated tumor cells in patients, where bio-molecular imaging has become an indispensable tool. Being one of many different imaging techniques, optical fluorescence imaging has been translated over the years from the bench to clinical research, and it is now on the verge of being able to address some of the pressing challenges in molecular oncology. Optical imaging can provide real-time, high spatially and temporally resolved detection of small cancer foci or establishment of boundaries between malignant and normal tissue during surgery, which is the primary treatment modality for most solid tumors. Furthermore, optical signals can provide information on tumor metabolism and biochemistry that helps provide an understanding of tumors at the molecular level, so as to gain access to the activity of their biological processes that may yield the capability to provide personalized “on the spot” treatment.Thus, advancing development of new optical fluorescent probes for imaging techniques has grown exponentially over the years, as these probes continue to revolutionize the ability to visualize complex biological processes in living systems. Fluorophores have been used in a wide variety of applications, ranging from medical diagnostic applications as chemical sensors and molecular probes, to display devices and dye-sensitized solar cells. Although extensive research work has been done on the development of molecular imaging probes, their use in the clinical setting is still in its infancy. The number of profluorophores that can have their fluorescence signature selectively and quickly altered by the presence of a disease-associated enzyme is extremely small, as is the type of disease-associated enzyme used for probe activation. The goal of this thesis is development of a group of small molecule-based profluorogenic probes and demonstration of their activity with a cancer-associated enzyme, NAD(P)H:quinone oxidoreductase-1 (NQO1). This goal was attained by completing several different objectives that will be discussed together with their outcomes in the following chapters of this dissertation.
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Hettiarachchi, Suraj Uditha, "Design, Synthesis, and Evaluation of Small Molecule-based, Profluorogenic Activatable Substrate Probes for Detection and Visualization of Human Cancer Enzyme NAD(P)H:Quinone Oxidoreductase-1" (2014). LSU Doctoral Dissertations. 3269.
McCarley, Robin L.