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。 治疗几种癌症，包括头部和颈部癌症。这一确定是例行执行的 通过前哨淋巴结活组织检查。虽然被广泛接受并被证明有效，但哨兵 淋巴结活检术存在一定的缺陷。这是一种侵入性的外科手术，可以导致 对于小于2毫米的不良事件和转移，通常不会被发现。这些小的转移瘤 已被证明在疾病的发展过程中有影响。因此，接受哨兵手术的患者 淋巴结活检可能会得到一个不太理想的治疗方案。在这个项目中，我们将开发一种非侵入性 以超声为基础的分子成像工具，以识别淋巴管中的微转移。我们将发展 定向偶联靶向细胞表面受体的全氟碳纳米微滴造影剂 抗体。我们将合成两种不同沸点和分子的纳米液滴 目标。一种纳米液滴制剂将靶向表皮生长因子受体(EGFR)，以使 分子检测癌细胞，而另一种则将作为非靶向的传递控制。基于 在超声图像中可视化的相变行为，我们将区分靶向EGFR的 纳米液滴与非特异性对照。然后，我们将应用比率和动力学建模策略来使用 不同的聚集模式，以突出转移较小的区域。纳米液滴及其成像 在将双示踪剂设计应用于小动物之前，将在聚丙烯酰胺模体中测试这些方法 头颈部癌转移模型的建立。总体结果将是一种方法，可以检测到小口袋的 淋巴管转移到几厘米深的组织中。

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.