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

项目摘要 确定肿瘤是否已经扩散到区域淋巴结对于分期和治疗计划至关重要 包括头颈部癌症在内的几种癌症。该测定是常规进行的 进行前哨淋巴结活检虽然被广泛接受并证明是有效的， 淋巴结活组织检查过程存在一些缺点。这是一种侵入性的外科手术， 小于2 mm的转移通常未被发现。这些小的转移瘤 被证明对疾病的发展有影响。因此，接受哨兵治疗的患者 淋巴结活组织检查可能接受次优治疗计划。在这个项目中，我们将开发一种非侵入性的 超声为基础的分子成像工具，以确定微转移在乳腺癌。我们将开发 通过定向缀合靶向细胞表面受体的全氟化碳纳米液滴造影剂 抗体的我们将合成两类纳米液滴，每一类都具有不同的沸点和分子量。 目标一种纳米液滴制剂将靶向表皮生长因子受体（EGFR）， 分子检测癌细胞，而另一种将作为非靶向控制传递。基于 在超声图像中可视化的相变行为，我们将区分EGFR靶向 纳米液滴和非特异性对照。然后，我们将应用比率和动力学建模策略， 不同的积聚模式以突出具有小转移的区域。纳米液滴和成像 在将双示踪剂设计应用于小动物之前，将在聚丙烯酰胺体模中测试方法 头颈癌转移模型。总体结果将是一种可以检测小口袋的方法 在组织中几厘米深的淋巴结转移。

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.