Exploiting Melanin Synthesis to Improve Tumor Detection with Multispectral Optoacoustic Tomography and Optical Guided Surgery

利用多光谱光声断层扫描和光引导手术利用黑色素合成来改善肿瘤检测

基本信息

  • 批准号:
    10152589
  • 负责人:
  • 金额:
    $ 20.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-05-01 至 2022-08-31
  • 项目状态:
    已结题

项目摘要

Our goal is to improve the localization of solid tumors that express and secrete high levels of protease enzymes. Proteases degrade the extracellular matrix and cellular stroma, increasing tumor proliferation, invasion, and metastasis. Our research will focus on the detection of tumors with cathepsin B and urokinase Plasminogen Activator, which are protease biomarkers of malignant tumors. Yet our technology can detect many types of proteases, and therefore can be a flexible platform technology for detecting many types of tumors. To meet our goal, we propose to develop a new type of contrast agent that is cleaved by a protease, then undergoes spontaneous disassembly, and finally spontaneously forms eumelanin or pheomelanin. Our contrast agents consist of peptides and melanins that are natural, biocompatible materials. Our spontaneous disassembling linkers are used for drug delivery, so that these linkers are also biocompatible. Therefore, our contrast agents have strong potential for eventual clinical translation. We propose to use our melanin-generating contrast agents to improve tumor localization with noninvasive Multispectral Optoacoustic Tomography (MSOT), also known as photoacoustic imaging. Pre-clinical MSOT can image an entire torso of mouse tumor models, and clinical MSOT has been used to image many tumor types including breast cancer. We will develop and use an innovative dynamic MSOT imaging protocol that will monitor the generation of melanins in tumors, which improves the specificity of protease-active tumors vs. normal tissues. We also propose to use our melanin-generating contrast agents to improve tumor localization during surgery. Other research has developed fluorescent contrast agents that are trapped or activated in tumors with high protease activity. These tumors can then be visualized during surgery, when the tumors can be imaged with fluorescence imaging instrumentation. Our technology will cause melanins to accumulate in tumors with high protease activity, causing the tumors to become black. Simple visual inspection, without expensive and cumbersome fluorescence imaging instrumentation, can identify the black tumors against the beige-to-red background of normal tissues. These black tumors can then be excised from the body during surgery. As a longer-term goal, we propose that MSOT could eventually be used to localize protease-active tumors as deep as 3 cm from tissue surfaces that are exposed during surgery, further improving surgical resection of tumors. To meet our objectives, we will synthesize each contrast agent, demonstrate that cleavage with a specific enzyme results in synthesis of a melanin, and perform Michaelis-Menten enzyme kinetics studies to validate the detection of enzyme activity. For Aim 1, we will perform in vivo MSOT studies to detect protease activities in mouse models of human tumors. For Aim 2, we will simulate optical guided surgery with mouse tumor models to detect black tumors that have high melanin accumulation. Our deliverable is a foundation for pursuing clinical translation of our contrast agents for clinical MSOT exams and during clinical surgery.
我们的目标是改善表达和分泌高水平蛋白酶的实体瘤的定位

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Mark David Pagel其他文献

Mark David Pagel的其他文献

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{{ truncateString('Mark David Pagel', 18)}}的其他基金

Exploiting Melanin Synthesis to Improve Tumor Detection with Multispectral Optoacoustic Tomography and Optical Guided Surgery
利用多光谱光声断层扫描和光引导手术利用黑色素合成来改善肿瘤检测
  • 批准号:
    9978211
  • 财政年份:
    2020
  • 资助金额:
    $ 20.25万
  • 项目类别:
Measuring Tumor Acidosis with PET/MRI Contrast Agents
使用 PET/MRI 造影剂测量肿瘤酸中毒
  • 批准号:
    9750458
  • 财政年份:
    2019
  • 资助金额:
    $ 20.25万
  • 项目类别:
Early phase clinical trial for imaging tumor acidosis in breast cancer patients using acidoCEST MRI
使用 AcidoCEST MRI 对乳腺癌患者肿瘤酸中毒进行成像的早期临床试验
  • 批准号:
    8948796
  • 财政年份:
    2015
  • 资助金额:
    $ 20.25万
  • 项目类别:
Detection of in vivo enzyme activities with CEST MRI
使用 CEST MRI 检测体内酶活性
  • 批准号:
    8495297
  • 财政年份:
    2012
  • 资助金额:
    $ 20.25万
  • 项目类别:
Measuring extracellular pH in pre-clinical tumor models with CEST MRI
使用 CEST MRI 测量临床前肿瘤模型中的细胞外 pH 值
  • 批准号:
    8446309
  • 财政年份:
    2012
  • 资助金额:
    $ 20.25万
  • 项目类别:
Measuring extracellular pH in pre-clinical tumor models with CEST MRI
使用 CEST MRI 测量临床前肿瘤模型中的细胞外 pH 值
  • 批准号:
    8286741
  • 财政年份:
    2012
  • 资助金额:
    $ 20.25万
  • 项目类别:
Detection of in vivo enzyme activities with CEST MRI
使用 CEST MRI 检测体内酶活性
  • 批准号:
    8852091
  • 财政年份:
    2012
  • 资助金额:
    $ 20.25万
  • 项目类别:
Measuring extracellular pH in pre-clinical tumor models with CEST MRI
使用 CEST MRI 测量临床前肿瘤模型中的细胞外 pH 值
  • 批准号:
    8817152
  • 财政年份:
    2012
  • 资助金额:
    $ 20.25万
  • 项目类别:
Detection of in vivo enzyme activities with CEST MRI
使用 CEST MRI 检测体内酶活性
  • 批准号:
    8353415
  • 财政年份:
    2012
  • 资助金额:
    $ 20.25万
  • 项目类别:
Detection of in vivo protease activities using PARACEST MRI contrast agents
使用 PARACEST MRI 造影剂检测体内蛋白酶活性
  • 批准号:
    7451742
  • 财政年份:
    2008
  • 资助金额:
    $ 20.25万
  • 项目类别:

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