Identification of cancer spread to tumor-draining lymph nodes through lymph node dissection and histology offers critical information for... Show moreIdentification of cancer spread to tumor-draining lymph nodes through lymph node dissection and histology offers critical information for guiding treatment in many cancer types, including breast, melanoma, head and neck, lung and gynecologic cancers, as the lymphatic system serves as the primary route for metastasis. Lymph node biopsy involves localization of tumor-draining lymph nodes, followed by their surgical removal and histological assessment. However, the procedure is associated with overtreatment concerns and some considerable morbidity, including lymphedema, seroma formation, and restricted arm movement. Moreover, conventional histological analyses are time-consuming and laborious, yet pathologists generally examine less than 1% of the volume of each lymph node, leading to undetected micrometastasis (tumor clusters 0.2-2mm in diameter) in 30-60% of cases. In response to these limitations in standard lymph node dissection protocol, there is a significant need for the development of lymph node imaging strategies that are capable of identifying metastatic cancer as a means of staging a patient’s cancer without the need for invasive and time-intensive conventional pathology. Paired-agent imaging molecular imaging protocols have been spearheaded by our group and entail co-administration of a control imaging agent with a molecular targeted agent as a way to account for nonspecific uptake and retention. The overall goal of my thesis was to methodically design, optimize and evaluate the clinical utility of a paired-agent lymph node imaging protocol to achieve levels of sensitivity and specificity in nodal staging not possible with current conventional methods, less invasively and at a fraction of the time and cost. Show less