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

用于检测头颈部淋巴结微转移的多重超声成像

• 批准号: 10870266
• 负责人: Geoffrey P. Luke
• 金额: $ 54.64万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-24 至 2024-08-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10870266
• 关键词: Acoustics; Address; Adverse event; Affect; Animal Model; Antibodies; Behavior; Binding; Biological; Cancer Detection; Cell Surface Receptors; Cells; Cervical lymph node group; Characteristics; Clinical; Clinical Research; Contrast Media; Deposition; Detection; Diagnosis; Disease; Disease Progression; Distant Metastasis; Drainage procedure; Elements; Epidermal Growth Factor Receptor; Evaluation; Excision; Exhibits; Exposure to; Fluorescence; Fluorocarbons; Focused Ultrasound Therapy; Formulation; Gases; Goals; Head and Neck Cancer; Head and Neck Neoplasms; Image; Imaging Device; Imaging Techniques; Immunoglobulin G; In Vitro; Injections; Invaded; Kinetics; Label; Liquid substance; Lymph Node of Head, Face and Neck; Lymphatic; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Metastatic Neoplasm to Lymph Nodes; Methods; Micrometastasis; Molecular; Molecular Target; Morbidity - disease rate; Morphology; Neoplasm Metastasis; Operative Surgical Procedures; Optics; Patients; Pattern; Penetration; Phagocytes; Phase Transition; Physicians; Physiologic pulse; Population; Positron-Emission Tomography; Primary Neoplasm; Procedures; Prognosis; Sampling Errors; Sensitivity and Specificity; Sentinel Lymph Node Biopsy; Signal Transduction; Site; Specificity; Staging; Survival Rate; Techniques; Testing; Tissues; Tracer; Transducers; Tumor Burden; Ultrasonic Transducer; Ultrasonography; Visualization; Work; aggressive therapy; antibody conjugate; behavior change; cancer cell; cancer type; clinical application; clinical translation; design; detection limit; draining lymph node; effective therapy; fluorescence imaging; fluorophore; head and neck cancer patient; histological specimens; image processing; imaging detection; imaging modality; imaging system; improved; kinetic model; lymph nodes; malignant mouth neoplasm; meter; migration; molecular imaging; mouse model; multiplexed imaging; nanoDroplet; non-invasive imaging; optical imaging; phase change; polyacrylamide; preclinical study; ratiometric; response; soft tissue; standard of care; targeted agent; treatment planning; treatment strategy; tumor; ultrasound

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.

项目概要 确定肿瘤是否已扩散到区域淋巴结对于分期和治疗计划至关重要 适用于多种癌症，包括头颈癌。该测定按常规进行 通过前哨淋巴结活检程序。虽然被广泛接受并被证明是有效的，但哨兵 淋巴结活检程序存在一些缺点。这是一种侵入性外科手术，可能会导致 不良事件和小于 2 毫米的转移通常未被发现。这些小转移瘤有 已被证明对疾病的进展有影响。因此，接受前哨检查的患者 淋巴结活检可能会收到次优的治疗计划。在这个项目中，我们将开发一种非侵入性的 基于超声的分子成像工具可识别淋巴管中的微转移。我们将开发 全氟化碳纳米液滴造影剂通过定向结合靶向细胞表面受体 抗体。我们将合成两类纳米液滴，每种纳米液滴具有不同的沸点和分子 目标。一种纳米液滴制剂将靶向表皮生长因子受体（EGFR），以实现 癌细胞的分子检测，而另一种则作为非靶向的传递控制。基于 通过超声图像中可视化的相变行为，我们将区分 EGF​​R 靶向的 纳米液滴和非特异性控制。然后，我们将应用比例和动力学建模策略来使用 不同的积累模式突出显示有小转移的区域。纳米液滴和成像 在将双示踪剂设计应用于小动物之前，将在聚丙烯酰胺模型中测试方法 头颈癌转移模型。总体结果将是一种可以检测小块的方法 淋巴管中的转移灶深达组织几厘米。