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

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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 through a sentinel lymph node biopsy procedure. While widely accepted and proven to be effective, the sentinel lymph node biopsy procedure suffers from some shortcomings. It is an invasive surgical procedure that can lead to adverse events and metastases smaller than 2 mm routinely go undetected. These small metastases have been shown to have implications in the progression of the disease. Thus, patients who undergo the sentinel lymph node biopsy 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.