Multiplex Ultrasound Imaging for the Detection of Head and Neck Lymph Node Micrometastases

Project Summary Determining whether a tumor has spread to the regional lymph nodes is critical for staging and treatment planning for several types of cancer, including cancers of the head and neck. This determination is routinely performed surgical removal of regional nodes for cancers of the head & neck. While widely accepted and proven to be effective for tumor staging and limiting the further spread of the disease, surgical removal of lymph nodes can lead to morbidity and small metastatic deposits may remain undetected due to pathological sampling error. Thus, patients who undergo the procedure may receive a suboptimal treatment plan. In this project, we will develop a noninvasive ultrasound-based molecular imaging tool to identify micrometastases in the lymphatics. We will develop perfluorocarbon nanodroplet contrast agents targeted to cell surface receptors via directional conjugation of antibodies. We will synthesize two classes of nanodroplets, each with a different boiling point and molecular target. One nanodroplet formulation will be targeted to the epidermal growth factor receptor (EGFR) to enable molecular detection of cancer cells, while the other will be untargeted to act as a delivery control. Based on the phase-change behavior visualized in ultrasound images, we will differentiate between the EGFR- targeted nanodroplets and the nonspecific control. Then, we will apply ratiometric and kinetic modeling strategies to use the different accumulation patterns to highlight regions with small metastases. The nanodroplets and imaging methods will be tested in polyacrylamide phantoms before the dual tracer design is applied to a small animal model of head and neck cancer metastasis. The overall result will be a method that can detect small pockets of metastases in the lymphatics several centimeters deep in tissue.