In Vivo Characterization and Quantification of Myelin in the Central Nervous Syst

中枢神经系统髓磷脂的体内表征和定量

基本信息

  • 批准号:
    7693687
  • 负责人:
  • 金额:
    $ 34.34万
  • 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:
    2008-09-30 至 2012-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The proposed research is aimed at developing radiopharmaceuticals that readily enter the brain and selectively localize in the white matter via direct binding to myelin membranes. Abnormality and changes associated with myelin membranes in the central nervous system play a key role in the pathogenesis of multiple sclerosis and other related neurodegenerative disorders. Thus, direct assessment of myelin content in vivo has been an important goal in protection and repair of axonal damage. However, the lack of molecular probes has limited the progress of myelin imaging and hindered efficacy evaluation of novel myelin repair therapies currently under development. To meet this need, we plan to develop myelin-imaging agents uniquely suited for use in clinical imaging modalities such as positron emission tomography (PET). We hypothesize that small-molecule PET probes can be developed, which will freely enter the brain, directly and selectively bind to myelin membranes. To test this hypothesis, we have identified some lead compounds with promising binding properties for in vivo studies, which allows us to address the following specific aims: 1) Rationally design and synthesize a selected series of myelin-imaging agents and quantitatively evaluate their binding properties in vitro for structure-activity relationship studies; 2) Radiolabel selected agents with positron-emitting 11C or 18F and assess the in vivo binding properties in animal models of demyelination to determine the rates of brain entry, clearance, and specific retention in the brain; 3) Evaluate the pharmacokinetic profiles and metabolism of selected myelin-imaging agents through PET studies in non-human primates for potential application in human subjects. It is anticipated that completion of the project will lead to the development of imaging markers that are suitable for application in human subjects. PUBLIC HEALTH RELEVANCE: This research project has following important impacts on public health: 1) facilitation of efficacy evaluation of therapies currently under development that are aimed at prevention of axonal damage and myelin repair; 2) direct correlation of myelin changes with clinical outcomes; 3) aid in early and accurate diagnosis and subtyping of MS and related diseases.
描述(由申请人提供):拟议的研究旨在开发易于进入大脑并通过直接结合髓鞘膜选择性定位于白质的放射性药物。中枢神经系统髓鞘膜的异常和改变在多发性硬化症和其他相关神经退行性疾病的发病机制中起关键作用。因此,体内髓磷脂含量的直接评估已成为轴突损伤保护和修复的重要目标。然而,分子探针的缺乏限制了髓磷脂成像的进展,阻碍了目前正在开发的新型髓磷脂修复疗法的疗效评估。为了满足这一需求,我们计划开发髓磷脂显像剂,专门用于临床成像模式,如正电子发射断层扫描(PET)。我们假设可以开发小分子PET探针,它将自由进入大脑,直接和选择性地结合髓鞘膜。为了验证这一假设,我们已经确定了一些具有良好结合特性的先导化合物,用于体内研究,这使我们能够解决以下具体目标:1)合理设计和合成一系列髓鞘显像剂,并定量评估其体外结合特性,用于结构-活性关系研究;2)用正电子发射11C或18F对选定的药物进行放射性标记,并评估脱髓鞘动物模型的体内结合特性,以确定脑内进入率、清除率和特异性滞留率;3)通过非人类灵长类动物的PET研究评估选定髓磷脂显像剂的药代动力学特征和代谢,以用于人类受试者的潜在应用。预计该项目的完成将导致适用于人类受试者的成像标记物的开发。公共卫生相关性:本研究项目对公共卫生有以下重要影响:1)促进目前正在开发的旨在预防轴突损伤和髓鞘修复的疗法的疗效评估;2)髓磷脂变化与临床预后的直接相关性;3)有助于MS及相关疾病的早期准确诊断和分型。

项目成果

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Yanming Wang其他文献

Yanming Wang的其他文献

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{{ truncateString('Yanming Wang', 18)}}的其他基金

In Vivo Characterization and Quantification of Myelin in the Central Nervous Syst
中枢神经系统髓磷脂的体内表征和定量
  • 批准号:
    7900404
  • 财政年份:
    2008
  • 资助金额:
    $ 34.34万
  • 项目类别:
In Vivo Characterization and Quantification of Myelin in the Central Nervous Syst
中枢神经系统髓磷脂的体内表征和定量
  • 批准号:
    7581860
  • 财政年份:
    2008
  • 资助金额:
    $ 34.34万
  • 项目类别:
In Vivo Characterization and Quantification of Myelin in the Central Nervous Syst
中枢神经系统髓磷脂的体内表征和定量
  • 批准号:
    8113314
  • 财政年份:
    2008
  • 资助金额:
    $ 34.34万
  • 项目类别:
Molecular Probes for In Vivo MR Studies of Myelin
用于髓磷脂体内 MR 研究的分子探针
  • 批准号:
    7295700
  • 财政年份:
    2006
  • 资助金额:
    $ 34.34万
  • 项目类别:
Molecular Probes for In Vivo MR Studies of Myelin
用于髓磷脂体内 MR 研究的分子探针
  • 批准号:
    7146860
  • 财政年份:
    2006
  • 资助金额:
    $ 34.34万
  • 项目类别:
Quantitative Imaging of Amyloid Deposits in AD and Aging
AD 和衰老中淀粉样蛋白沉积的定量成像
  • 批准号:
    7113688
  • 财政年份:
    2003
  • 资助金额:
    $ 34.34万
  • 项目类别:
Quantitative Imaging of Amyloid Deposits in AD and Aging
AD 和衰老中淀粉样蛋白沉积的定量成像
  • 批准号:
    6731822
  • 财政年份:
    2003
  • 资助金额:
    $ 34.34万
  • 项目类别:
Quantitative Imaging of Amyloid Deposits in AD and Aging
AD 和衰老中淀粉样蛋白沉积的定量成像
  • 批准号:
    7279281
  • 财政年份:
    2003
  • 资助金额:
    $ 34.34万
  • 项目类别:
Quantitative Imaging of Amyloid Deposits in AD and Aging
AD 和衰老中淀粉样蛋白沉积的定量成像
  • 批准号:
    6946911
  • 财政年份:
    2003
  • 资助金额:
    $ 34.34万
  • 项目类别:
Quantitative Imaging of Amyloid Deposits in AD and Aging
AD 和衰老中淀粉样蛋白沉积的定量成像
  • 批准号:
    6805319
  • 财政年份:
    2003
  • 资助金额:
    $ 34.34万
  • 项目类别:

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