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: 8620654
• 负责人: STANISLAV Y EMELIANOV
• 金额: $ 55.19万
• 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/8620654
• 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; 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; photoacoustic imaging; 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.

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是至关重要的。不幸的是，没有实时的，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，临床上迫切需要一种成像技术，其广泛可用、非侵入性且操作简单、安全，并且可以可靠地检测和真实的充分诊断淋巴结微转移。 我们研究计划的总体目标是开发一种先进的、体内的、非侵入性的、分子特异性成像技术，即，集成的超声和光声成像结合靶向等离子体纳米传感器，能够真实的实时立即准确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集成是可能的，并且超声和光声成像都可以在真实的时间内进行，从而产生即时诊断并允许早期实施治疗。 一系列科学和工程，生物医学和临床问题必须得到解决，以充分探索分子特异性超声和光声淋巴（MS-USPAL）成像的前哨淋巴结微转移的检测和表征的能力。目前的应用集中在MS-USPAL成像的临床翻译的重要方面。我们将为MS-USPAL开发和验证临床可翻译的等离子体纳米传感器。我们将使用超小的金纳米颗粒靶向表皮生长因子受体（EGFR），这是过度表达的鳞状细胞癌和许多其他上皮肿瘤。对于癌细胞的高灵敏度检测，我们将探索EGF受体介导的内吞作用和紧密间隔的分子特异性纳米颗粒之间的等离子体共振耦合的效果。纳米颗粒的超小尺寸将非常有利于从体内快速清除，这将允许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（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，我们将设计和构建一个原型的临床MS-USPAL成像系统能够在体内成像5 nm的纳米粒子。