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

基本信息

  • 批准号:
    7451742
  • 负责人:
  • 金额:
    $ 20.39万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-08-01 至 2010-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Proteases are important biomarkers for many pathologies and biological processes and are often targets of chemotherapeutics. Magnetic Resonance Imaging (MRI) is an outstanding diagnostic tool for identifying suspicious lesions, but suffers from many false-positive results due to a lack of specificity for pathological tissues versus normal tissues. The development of MRI contrast agents that can detect protease biomarkers of metastatic tumors or the response to anti-tumor therapies would greatly improve the specificity of MRI for detecting and evaluating cancer. We have developed a fundamentally new type of protease-responsive MRI contrast agent that is detected through PARAmagnetic Chemical Exchange Saturation Transfer (PARACEST). This mechanism allows each PARACEST contrast agent to be selectively detected, so that multiple PARACEST contrast agents may be simultaneously detected during a single MRI scan session, such as a protease-unresponsive PARACEST contrast agent that can serve as a `control' to account for the pharmacokinetics of the agents. Furthermore, we are the first research team to demonstrate the detection of PARACEST contrast agents within in vivo animal models. We will combine our accomplishments with PARACEST contrast agents to detect multiple enzyme-responsive PARACEST contrast agents within in vivo animal models. More specifically, we will design and apply PARACEST contrast agents to detect caspase-3 during TRAIL-induced tumor cell apoptosis in an in vivo mouse model of MCF-7c3 human mammary carcinoma. We will also design and apply PARACEST contrast agents to simultaneously detect cathepsin B and urokinase Plasminogen Activator in an in vivo mouse model of MCF-7 and MBA-MB-231 mammary carcinoma. The successful achievement of our specific aims will result in new platform technology that can be immediately used during many pre-clinical studies, and that can be used as a foundation for further studies to gain clinical approval for this new type of diagnostic molecular imaging agent to detect protease biomarkers in cancer and other pathological tissues. Narrative: A fundamentally new type of protease-responsive MRI contrast agent has been developed that is detected through PARAmagnetic Chemical Exchange Saturation Transfer (PARACEST). Furthermore, PARACEST contrast agents can be detected within in vivo animal models. This research application will combine these accomplishments with PARACEST contrast agents to detect multiple enzyme-responsive PARACEST contrast agents within in vivo animal models.
描述(由申请人提供):蛋白酶是许多病理学和生物学过程的重要生物标志物,通常是化疗药物的靶标。磁共振成像(MRI)是用于识别可疑病变的杰出诊断工具,但由于对病理组织与正常组织缺乏特异性而遭受许多假阳性结果。能够检测转移性肿瘤的蛋白酶生物标志物或对抗肿瘤治疗的反应的MRI造影剂的开发将大大提高MRI用于检测和评估癌症的特异性。我们开发了一种全新的蛋白酶响应型MRI造影剂,通过顺磁化学交换饱和转移(PARACEST)进行检测。这种机制允许选择性地检测每种PARACEST造影剂,从而在单个MRI扫描期间可以同时检测多种PARACEST造影剂,例如可以用作“对照”以说明试剂的药代动力学的蛋白酶无响应PARACEST造影剂。此外,我们是第一个证明在体内动物模型中检测PARACEST造影剂的研究团队。我们将联合收割机与PARACEST造影剂结合,在体内动物模型中检测多种酶反应性PARACEST造影剂。更具体地说,我们将设计和应用PARACEST造影剂,以检测在体内MCF-7 c3人乳腺癌小鼠模型中TRAIL诱导的肿瘤细胞凋亡过程中的caspase-3。我们还将设计和应用PARACEST造影剂,在MCF-7和MBA-MB-231乳腺癌的体内小鼠模型中同时检测组织蛋白酶B和尿激酶纤溶酶原激活剂。我们特定目标的成功实现将产生新的平台技术,可以在许多临床前研究中立即使用,并可用作进一步研究的基础,以获得这种新型诊断分子成像剂的临床批准,以检测癌症和其他病理组织中的蛋白酶生物标志物。叙述:一种全新的蛋白酶响应型MRI造影剂已被开发出来,通过顺磁化学交换饱和转移(PARACEST)进行检测。此外,可以在体内动物模型中检测到PARACEST造影剂。该研究应用将联合收割机这些成就与PARACEST造影剂结合,以检测体内动物模型中的多种酶响应性PARACEST造影剂。

项目成果

期刊论文数量(0)
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科研奖励数量(0)
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:
    $ 20.39万
  • 项目类别:
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:
    10152589
  • 财政年份:
    2020
  • 资助金额:
    $ 20.39万
  • 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:
    $ 20.39万
  • 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:
    $ 20.39万
  • 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:
    $ 20.39万
  • 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:
    $ 20.39万
  • 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:
    $ 20.39万
  • 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:
    $ 20.39万
  • 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:
    $ 20.39万
  • 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:
    $ 20.39万
  • 项目类别:

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