Evaluation of Near-Infrared Contrast Agents for Cancer Detection using Optical Imaging Techniques

Breast cancer is the second most common type of cancer among women, with an estimated 2.8 million diagnosed in the United States. Many cancers cannot be detected by their intrinsic vascular contrast, especially in their early stages. This necessitates the use of an exogenous contrast agent. Photoacoustic Imaging (PAI) and Fluorescence imaging (FI) are promising non-invasive in vivo cancer diagnostic methods. To further improve the tumor to background contrast, researchers are investigating various exogenous contrast agents for PAI and fluorescence imaging that target tumor vasculature and hypoxia. This dissertation is structured into two main sections. In the first part, the evaluation of several novel porphyrin dyes has been presented as PAI contrast agents in direct comparison to the commonly used indocyanine green (ICG). Imaging of a sub-mm target containing quinoline-annulated porphyrin up to 2 cm depth in a tissue-like matrix exceeds the performance of imaging the similar target containing ICG, which suggests the use of quinoline-annulated porphyrins as potential contrast agents for cancer detection using PAI. The second part of the dissertation reports an investigation of the unsubstituted imidazole derivative as well as the 4-nitroimidazole ICG-conjugate for targeting tumor hypoxia. The performance of 4-nitroimidazole dye by imaging tumor cells in vitro and animals in vivo were validated, and the results with the 2-nitroimidazole dye were compared, using the imidazole derivative as the reference. The results demonstrated the efficacy of 4-nitroimidazole-ICG as a hypoxia targeting fluorescence probe and suggest the use of 4-nitroimidazole dye-conjugate as a hypoxia probe with a significant cost reduction in the synthesis.