Acoustic Imaging of Sentinel Node Matastasis using Plasmonic Nanosensors

使用等离子体纳米传感器对前哨淋巴结转移进行声学成像

• 批准号: 8311479
• 负责人: STANISLAV Y EMELIANOV
• 金额: $ 57.98万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8311479
• 关键词: Address; Algorithms; Animal Model; Animals; Antibodies; Binding; Binding Sites; Biodistribution; Biological; Biomedical Engineering; Cancer Patient; Cancerous; Cell Culture Techniques; Cells; Clinical; Coupling; Detection; Diagnosis; Diagnostic Imaging; Disseminated Malignant Neoplasm; Epidermal Growth Factor Receptor; Epithelial; Epithelial Cells; Epithelial Neoplasms; Feces; Funding; Goals; Gold; Head and neck structure; Human; Image; Image Analysis; Imaging Techniques; Imaging technology; Immune; Inflammation; Injection of therapeutic agent; Intravenous; Lasers; Left; Life; Ligands; Lymphatic; Lymphatic System; Lymphocyte; Malignant Neoplasms; Maps; Medical; Methods; Micrometastasis; Molecular; Monitor; Mus; Neoplasm Metastasis; Optics; Organ; Pathway interactions; Patients; Physiologic pulse; Primary Neoplasm; Property; Public Health; Research; Resected; Resolution; Sampling; Screening for cancer; Sensitivity and Specificity; Sentinel Lymph Node; Signal Transduction; Slide; Source; Specificity; Specimen; Squamous cell carcinoma; System; Techniques; Technology; Testing; Therapeutic; Time; Tissue Sample; Tissues; Toxic effect; Translations; Ultrasonic Transducer; Ultrasonics; Ultrasonography; Urine; Xenograft procedure; acoustic imaging; antigen binding; biomaterial compatibility; cancer cell; clinical practice; cost; cytotoxicity; design and construction; image processing; improved; in vivo; intraoperative imaging; lymph nodes; macrophage; molecular/cellular imaging; mouse model; nanoparticle; nanosensors; outcome forecast; overexpression; plasmonics; programs; prototype; receptor mediated endocytosis; research clinical testing; uptake

DESCRIPTION (provided by applicant): In cancer patients, determination of whether a malignancy has spread is the single most important factor used to develop a therapeutic plan and to predict prognosis. In most cases, cancer cells initially spread through regional lymph nodes. Therefore, clinical evaluation for the presence of regional lymph node metastases is of paramount importance. Unfortunately, there are no real-time, non-invasive clinical methods that can reliably detect and diagnose micrometastases in lymph nodes. Therefore, there is an urgent clinical need for an imaging technique that is widely available, is non-invasive and simple to perform, is safe, and can reliably detect and adequately diagnose lymph node micrometastases in real time. The overall goal of our research program is to develop an advanced, in-vivo, noninvasive, molecular specific imaging technology, i.e., integrated ultrasound and photoacoustic imaging combined with targeted plasmonic nanosensors, capable of immediate and accurate assessment of sentinel lymph node micrometastases in real time. The underlying hypothesis of this project is that photoacoustic imaging integrated with widely used clinical ultrasound imaging is possible and both ultrasound and photoacoustic imaging can be performed in real time, yielding an immediate diagnosis and allowing early implementation of treatment. A wide range of scientific and engineering, biomedical and clinical problems must be addressed to fully explore the capabilities of molecular specific ultrasound and photoacoustic lymphatic (MS-USPAL) imaging in detection and characterization of sentinel lymph node micrometastases. The current application is focused on important aspects of clinical translation of MS-USPAL imaging. We will develop and validate clinically translatable plasmonic nanosensors for MS-USPAL. We will use ultra-small gold nanoparticles to target epidermal growth factor receptor (EGFR), which is overexpressed in squamous carcinoma and in many other epithelial neoplasms. For highly sensitive detection of cancer cells, we will explore EGF receptor mediated endocytosis and the effect of plasmon resonance coupling between closely spaced molecular specific nanoparticles. The ultra-small size of nanoparticles will be highly favorable for rapid clearance from the body which will allow safe transition into clinical practice Additionally, 5 nm ligand capped gold nanoparticles will greatly reduce nonspecific interactions and reduce the uptake of nanoparticles by immune cells such as macrophages present due to lymph node inflammation, thus diminishing false positive results. Furthermore, we will design and construct a prototype of the clinical MS-USPAL imaging system capable of imaging 5 nm nanoparticles in-vivo. PUBLIC HEALTH RELEVANCE: In cancer patients, the determination of the spread of malignancy is the single most important factor to develop a therapeutic plan and predict prognosis. In most cases, cancer cells initially spread through regional lymph nodes. Thus, a technology such as molecular specific ultrasound and photoacoustic lymphatic imaging, capable of in-vivo, noninvasive and accurate assessment of regional metastases in real time, can simplify and improve management of patients with epithelial malignancies, significantly improve public health, and reduce medical costs.

描述（由申请人提供）：在癌症患者中，确定恶性肿瘤是否已扩散是用于制定治疗计划和预测预后的最重要因素。在大多数情况下，癌细胞最初通过区域淋巴结扩散。因此，临床评估区域淋巴结转移的存在至关重要。不幸的是，没有实时、非侵入性的临床方法可以可靠地检测和诊断淋巴结中的微转移。因此，临床迫切需要一种可广泛使用、非侵入性、操作简单、安全、能够可靠地实时检测和充分诊断淋巴结微转移的成像技术。 我们研究计划的总体目标是开发一种先进的体内、无创、分子特异性成像技术，即集成超声和光声成像与靶向等离子体纳米传感器相结合，能够实时、准确地评估前哨淋巴结微转移。该项目的基本假设是，光声成像与广泛使用的临床超声成像相结合是可能的，并且超声和光声成像都可以实时进行，从而立即诊断并允许早期实施治疗。 必须解决广泛的科学和工程、生物医学和临床问题，以充分探索分子特异性超声和光声淋巴管 (MS-USPAL) 成像在前哨淋巴结微转移的检测和表征中的能力。当前的应用集中于 MS-USPAL 成像临床转化的重要方面。我们将开发并验证用于 MS-USPAL 的临床可翻译等离子体纳米传感器。我们将使用超小的金纳米粒子来靶向表皮生长因子受体（EGFR），该受体在鳞状癌和许多其他上皮肿瘤中过度表达。为了高度灵敏地检测癌细胞，我们将探索 EGF 受体介导的内吞作用以及紧密排列的分子特异性纳米粒子之间的等离振子共振耦合的影响。纳米颗粒的超小尺寸将非常有利于从体内快速清除，从而安全过渡到临床实践。此外，5 nm配体封端的金纳米颗粒将大大减少非特异性相互作用，并减少免疫细胞（例如由于淋巴结炎症而存在的巨噬细胞）对纳米颗粒的摄取，从而减少假阳性结果。此外，我们将设计并构建能够对 5 nm 纳米粒子进行体内成像的临床 MS-USPAL 成像系统原型。 公共卫生相关性：在癌症患者中，确定恶性肿瘤的扩散是制定治疗计划和预测预后的最重要因素。在大多数情况下，癌细胞最初通过区域淋巴结扩散。因此，分子特异性超声和光声淋巴成像等技术能够对局部转移进行体内、无创、准确的实时评估，可以简化和改善上皮恶性肿瘤患者的治疗，显着改善公众健康，并降低医疗成本。