A theranostic approach for risk stratification and intervention of deep vein thrombosis.

深静脉血栓形成风险分层和干预的治疗诊断方法。

基本信息

项目摘要

Summary Data suggest that 60,000-100,000 Americans die of venous thromboembolism (VTE) each year, that 50% of the surviving patients will have long-term complications, and that about one third of the survivors have recurrence within 10 years. The US healthcare costs are staggering and carry a high burden for treatment of VTE patients; it is estimated that $10 billion US dollars are spent each year accounting for treatment and man- agement of VTE. There is a critical need for both, accurate clinical diagnosis of VTE, in particular deep vein thrombosis (DVT), and targeted therapies to reduce safety issues, specifically intracranial hemorrhage, asso- ciated with thrombolytic drugs. Current diagnostic methods are not accurate: blood test assessing D-dimer blood levels are only indicative of DVT. Imaging techniques such as X-ray venography and ultrasonography reflect changes in the venous anatomy, but these modalities do not provide information about the molecular composition of the thrombus. Only biopsy followed by histology gives the molecular information needed for ac- curate prognosis, but these methods are invasive and associated with significant risks. We propose a non- invasive, magnetic resonance imaging (MRI) approach using a targeted contrast agent to gain information of the thrombus molecular composition to aid prognosis. The probe will also be engineered to aid therapeutic in- tervention through disruption of disease-promoting pathways or drug delivery. The integrated imaging and therapeutic capabilities will also facilitate longitudinal follow-up to monitor disease progression and therapy success. We will target myeloid-related protein 14 (MRP-14,  also referred to as S100A9). MRP-14 is secreted from activated neutrophils, monocytes, and platelets and our data indicate a link between MRP-14 and DVT. MRP-14 is found at high levels in DVT and knockout of MRP-14 in mice attenuates DVT formation. Using a phage library combinatorial approach, we identified specific peptide ligands that target MRP-14 with high speci- ficity. We will integrate the MRP-14 binders with a macromolecular MRI contrast agent, and we will develop an MRI protocol for non-invasive detection of MRP-14 to aid diagnosis and prognosis of DVT. At the same time, we will develop a targeted therapeutic approach: first, we will test whether disruption of the MRP-14 function can attenuate DVT formation. Second, we will assess MRP-14 targeted delivery of the thrombolytic drug plas- minogen activator (tPA). The targeted therapeutic approach holds the potential to overcome bleeding risks as- sociated with the treatment. Disease progression and therapy success will be evaluated in a longitudinal MRI study.
总结

项目成果

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Nicole Franziska Steinmetz其他文献

Nicole Franziska Steinmetz的其他文献

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{{ truncateString('Nicole Franziska Steinmetz', 18)}}的其他基金

Dual-pronged nano-drug delivery using plant virus-like particles
使用植物病毒样颗粒的双管齐下纳米药物输送
  • 批准号:
    10700990
  • 财政年份:
    2022
  • 资助金额:
    $ 55.9万
  • 项目类别:
Dual-pronged nano-drug delivery using plant virus-like particles.
使用植物病毒样颗粒进行双管齐下的纳米药物输送。
  • 批准号:
    9982275
  • 财政年份:
    2018
  • 资助金额:
    $ 55.9万
  • 项目类别:
Dual-pronged nano-drug delivery using plant virus-like particles.
使用植物病毒样颗粒进行双管齐下的纳米药物输送。
  • 批准号:
    10224677
  • 财政年份:
    2018
  • 资助金额:
    $ 55.9万
  • 项目类别:
Dual-pronged nano-drug delivery using plant virus-like particles
使用植物病毒样颗粒的双管齐下纳米药物输送
  • 批准号:
    9372245
  • 财政年份:
    2017
  • 资助金额:
    $ 55.9万
  • 项目类别:
Diagnosis and longitudinal monitoring of metastatic prostate cancer through molecular MR imaging
通过分子磁共振成像诊断和纵向监测转移性前列腺癌
  • 批准号:
    9208751
  • 财政年份:
    2016
  • 资助金额:
    $ 55.9万
  • 项目类别:
Diagnosis and longitudinal monitoring of metastatic prostate cancer through molecular MR imaging.
通过分子磁共振成像诊断和纵向监测转移性前列腺癌。
  • 批准号:
    9755062
  • 财政年份:
    2016
  • 资助金额:
    $ 55.9万
  • 项目类别:
Diagnosis and longitudinal monitoring of metastatic prostate cancer through molecular MR imaging.
通过分子磁共振成像诊断和纵向监测转移性前列腺癌。
  • 批准号:
    9629935
  • 财政年份:
    2016
  • 资助金额:
    $ 55.9万
  • 项目类别:
Engineering 'Grapevine Virus A' filaments for nanomedical applications
工程“葡萄病毒 A”细丝用于纳米医学应用
  • 批准号:
    9144385
  • 财政年份:
    2015
  • 资助金额:
    $ 55.9万
  • 项目类别:
Detection of lethal prostate cancer with macromolecule-based, EGFL-7 targeted MR imaging approach
使用基于大分子的 EGFL-7 靶向 MR 成像方法检测致命性前列腺癌
  • 批准号:
    8954282
  • 财政年份:
    2015
  • 资助金额:
    $ 55.9万
  • 项目类别:
Detection of lethal prostate cancer with macromolecule-based, EGFL-7 targeted MR imaging approach
使用基于大分子的 EGFL-7 靶向 MR 成像方法检测致命性前列腺癌
  • 批准号:
    9094573
  • 财政年份:
    2015
  • 资助金额:
    $ 55.9万
  • 项目类别:

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Construction of affinity sensors using high-speed oscillation of nanomaterials
利用纳米材料高速振荡构建亲和传感器
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