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Optical labeling of tumor boundaries

肿瘤边界的光学标记

基本信息

批准号：
7140109
负责人：
GREGORY W FARIS
金额：
$ 19.04万
依托单位：
SRI INTERNATIONAL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-28 至 2009-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7140109
关键词：
bioimaging /biomedical imaging biomedical equipment development cell line chemical synthesis cyanine disease /disorder model dyes enzyme substrate infrared microscopy laboratory rat molecular /cellular imaging neoplastic cell optics protein glutamine gamma glutamyltransferase technology /technique development

项目摘要

DESCRIPTION (provided by applicant): Detection and monitoring of tumor boundaries are vital for the effective treatment of cancer and for improving our understanding of cancer progression. Recent studies by SRI International's (SRI's) collaborators have identified an enzyme, tissue transglutaminase (tTG) that demarcates the border between normal and injured/malignant tissue. SRI hypothesizes that the activity of this enzyme can be exploited to outline tumors using optical detection. To test this hypothesis, SRI proposes an R21 project with the following specific aims: (1) Modify optical instrumentation for in vitro assays and in vivo imaging using optically labeled tTG substrates. We will modify a fluorescence microscope and in vivo imaging system design to use appropriate excitation and emission wavelengths for the labeled substrates. (2) Synthesize and evaluate plasma protein-based tTG substrates with optical labels. Substrates acted on by tTG will be conjugated with cyanine dyes suitable for near-infrared in vivo imaging. Labeled substrate will be evaluated in an in vitro assay on an endothelial cell line. (3) Test activity on labeled substrates in vivo using infrared imaging. This imaging will be performed on a wound-healing model, a substrate clearance model, and a tumor model in rats. In the longer term, we plan to use labeled tTG substrates to answer basic questions regarding tumor progression and to develop a methodology for clinical demarcation of tumor boundaries suitable for use as an intraoperative diagnostic during biopsy or tumor removal. The technique would also be of value for imaging thrombi.

描述（由申请人提供）：肿瘤边界的检测和监测对于有效治疗癌症和提高我们对癌症进展的理解至关重要。SRI国际（SRI）合作者最近的研究已经确定了一种酶，组织转氨酶（tTG），它可以划分正常和受伤/恶性组织之间的边界。SRI假设这种酶的活性可以利用光学检测来勾画肿瘤。为了检验这一假设，SRI提出了一个R21项目，其具体目标如下： (1)使用光学标记的tTG底物修改用于体外测定和体内成像的光学仪器。我们将修改荧光显微镜和体内成像系统的设计，使用适当的激发和发射波长的标记基板。 (2)合成和评价具有光学标记的基于血浆蛋白的tTG底物。通过tTG作用的底物将与适合于近红外体内成像的花青染料缀合。将在内皮细胞系的体外试验中评价标记底物。 (3)使用红外成像在体内测试标记底物的活性。该成像将在大鼠的伤口愈合模型、底物清除模型和肿瘤模型上进行。从长远来看，我们计划使用标记的tTG底物来回答有关肿瘤进展的基本问题，并开发一种适用于活检或肿瘤切除过程中术中诊断的肿瘤边界临床划分方法。该技术对于血栓成像也很有价值。