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Functional Imaging of Tumor-Associated Lymphatics

肿瘤相关淋巴管的功能成像

基本信息

批准号：
8435339
负责人：
Sunkuk Kwon
金额：
$ 15.33万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-03-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8435339
关键词：
Acceleration Adjuvant Architecture Biopsy Blocking Antibodies Clinical Clinical Trials Critical Pathways Data Diagnostic Diagnostic Neoplasm Staging Disseminated Malignant Neoplasm Drainage procedure Evaluation Experimental Animal Model Fluorescence Foundations Functional Imaging Image Imaging Techniques Indocyanine Green Institutes Lead Lymph Lymph Node Involvement Lymphangiogenesis Lymphatic Lymphatic System Lymphatic vessel Malignant Neoplasms Metastatic Neoplasm to Lymph Nodes Methods Modeling Molecular Medicine Morbidity - disease rate Mus Neoplasm Metastasis Nodal Pathway interactions Pattern Permeability Phenotype Process Prognostic Marker Research Research Proposals Role Route Staging Testing Therapeutic Therapeutic Intervention Time Transgenic Organisms Translating Translations Tumor Cell Line Vascular Endothelial Growth Factor Receptor Work Xenograft procedure base bevacizumab cancer cell clinical practice fluorescence imaging fluorophore implantation in vivo intradermal injection lymph flow lymph nodes malignant breast neoplasm melanoma neutralizing antibody novel diagnostics novel therapeutics pre-clinical response subcutaneous therapeutic target tumor tumor growth tumor progression

项目摘要

DESCRIPTION (provided by applicant): Lymphatic invasion is a major route for the spread of metastatic cancer cells. Yet despite the important role of lymphatics as a critical pathway for cancer metastasis, relatively little is known about tumor-associated lymphatic function, due in part to the inability to directly image the lymphatics in vivo. Recently, we demonstrated for the first time the ability to non-invasively and quantitatively image lymphatic contractile function in mice using dynamic near-infrared (NIR) fluorescence imaging with intradermal injection of a nonspecific NIR fluorophore, indocyanine green (ICG). Subsequently, the same approach was employed in mice with extensive lymph node (LN) metastasis to image alteration of lymphatic drainage pathways and lymphatic contractile activity. Based upon our initial findings, we propose to use non-invasive, dynamic functional NIR fluorescence imaging to longitudinally image tumor-associated lymphatics to test our working hypothesis that cancer metastasis is accompanied by transient changes of lymphatic contractile function and lymph flow patterns. Specifically, our aims are to: 1. Image spatial and temporal changes in lymphatic contractile function and drainage pathways longitudinally in response to tumor growth and LN metastasis in different experimental animal models of cancer in order to elucidate whether aberrant lymphatic function and lymph flow patterns are a prognostic marker of metastasis and, 2. Image spatial and temporal changes of the lymphatics in response to the anti-VEGF receptor (VEGFR)-32. Image spatial and temporal changes of the lymphatics in response to the anti-VEGF receptor (VEGFR)-3 blocking antibody or a combination of anti-VEGFR-2 and -3 blocking antibodies as a means to ameliorate the earliest tumor lymphangiogenesis and reduce the rate of metastasis in tumor-bearing mice. This project, if successful, could motivate translation of a new diagnostic for tumor-node- metastasis (TNM) staging and acceleration of clinical trials of emerging therapeutics that target the lymphatics.

描述(申请人提供)：淋巴侵入是转移性癌细胞扩散的主要途径。然而，尽管淋巴管作为癌症转移的关键途径发挥着重要作用，但人们对肿瘤相关淋巴功能的了解相对较少，部分原因是无法在体内直接成像淋巴管。最近，我们首次展示了在皮内注射非特异性近红外荧光团吲哚青绿(ICG)的情况下，使用动态近红外(NIR)荧光成像非侵入性和定量成像小鼠淋巴收缩功能的能力。随后，在有广泛淋巴转移(LN)的小鼠上采用相同的方法来成像淋巴引流途径和淋巴收缩活动的改变。基于我们的初步发现，我们建议使用非侵入性的动态功能近红外荧光成像来纵向成像肿瘤相关的淋巴管，以验证我们的工作假设，即癌症转移伴随着淋巴管收缩功能和淋巴流动模式的瞬时变化。具体地说，我们的目的是：1.在不同的肿瘤生长和LN转移的实验动物模型中，成像淋巴管收缩功能和引流途径的纵向时空变化，以阐明异常的淋巴功能和淋巴流动模式是否是转移的预后标志；2.成像淋巴管对抗血管内皮生长因子受体(VEGFR)-32的响应的时空变化。抗血管内皮生长因子受体(VEGFR)-3阻断抗体或抗VEGFR-2和-3阻断抗体联合作用下淋巴管的时空变化可作为改善荷瘤小鼠最早的肿瘤淋巴管生成和降低转移率的手段。如果该项目成功，可能会推动肿瘤转移(TNM)分期的新诊断方法的翻译，并加速针对淋巴管的新兴疗法的临床试验。