There are millions of new head and neck cancers diagnosed each year, and it is one of the most aggressive cancers. The typical first line of... Show moreThere are millions of new head and neck cancers diagnosed each year, and it is one of the most aggressive cancers. The typical first line of therapy for head and neck cancers is surgery; however, if the cancer has spread (metastasized) from the primary tumor, more advanced surgery and/or adjuvant therapy (chemotherapy and or radiation therapy) can be indicated. Clinically, metastasis is diagnosed by surgically removing one or more lymph nodes draining the primary tumor during the primary tumor resection. Each lymph node located and removed adds to the morbidity of the procedure, so many clinics are moving toward a “sentinel” lymph node biopsy strategy, where only the first lymph node draining the tumor is removed and sent to pathology. Assessment of the node for cancer can take up to a week. If this lymph node is found to have cancer, the patient is then asked to return for a secondary surgery where a complete neck dissection is carried out (removal of all the lymph nodes in the side of the neck ipsilateral to the tumor). This delay in diagnosis is stressful on patients, adds health care costs, and considering the invasiveness of some primary tumor resections, some patients opt not to return for callback surgeries even though it would improve their chances of survival. This thesis presents efforts to test the ability for a fluorescence molecular imaging system called “agent-dependent enhanced photon tomography” (ADEPT) to be able to detect cancer in an excised sentinel lymph node while the patient is still on the operating table. This would allow a significant reduction in the number of patients requiring callback surgeries. Specifically, this thesis explores (in chapter 1) the development of a porcine lymph node fresh tissue model using implanted human cancer spheroids to act as realistic models of a freshly excised sentinel lymph node; (in chapter 2) the advancement of this tissue model to include a range of cancer burden levels and cancer cells strains; (and in chapter 3) a first demonstration of the ADEPT system applied to these realistic tissue models to detect clinically relevant levels of cancer. The ADEPT is a prototype designed specifically for the purpose of being faster in terms of processing and eliminates the need for patient to come back surgeries. We were able to validate ADEPT by incorporating a metastatic model mimicking a human lymph node and verifying the presence of cancer tumor that was manually injected into the lymph node followed by infusion of imaging agents. Show less
