Library Synthesis and Screening of Eu(II)-Based Contrast Agents

基于 Eu(II) 的造影剂的文库合成和筛选

基本信息

  • 批准号:
    10093042
  • 负责人:
  • 金额:
    $ 31.56万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-06-01 至 2023-02-28
  • 项目状态:
    已结题

项目摘要

There is a great need for contrast agents for magnetic resonance imaging (MRI) that respond to changes in redox environment to enable the facile monitoring of responses to new therapies, to guide cancer treatment selection, to image early responses for driving treatment development, and to enable the testing of hypotheses relevant to the collective fundamental understanding between redox environment and human health. The long- term goal of the research project is to develop positive contrast agents for MRI to fill this void in diagnostic medicine by focusing on EuII-containing complexes that are among the most promising areas of study. The overall objective of this application is to establish the groundwork necessary for translation of new Eu-based complexes into useful redox-responsive contrast agents by assembling and screening a library of EuII- and EuIII-containing complexes for their thermodynamic stability, kinetic inertness, and relaxivity. The rationale that underpins the proposed research is that EuII can be stabilized against oxidation and rendered non-toxic in vivo through ligand modification, as recently demonstrated; that the ideal ligand system will coordinate both EuII and EuIII; and that ligands that bind both oxidation states can be rationally designed with the information gained by studying a library of complexes. The expected outcome of this proposal is a great strengthening of the chemical foundation for the development of redox-responsive, Eu-based complexes for use as contrast agents in MRI. This outcome is expected to have a positive impact by contributing to the NIH's mission in the diagnosis of human diseases and development of new therapies. The objective of the proposal is expected to be achieved by pursuing three specific aims: (1) to assemble a library of ligands composed of synthesized cryptands and commercially available noncryptand ligands; (2) to screen ligands with EuII and with GdIII for T1- shortening indicative of complex formation; and (3) to characterize the thermodynamic stability, kinetic inertness, and relaxivity of EuII- and EuIII-containing complexes. The new Eu-based probes will be significant because they are expected to enable changes in redox environments resulting from therapies to be imaged, consequently, aiding in treatment development and selection and increasing the basic understanding of the relationship between redox homeostasis and human health. Furthermore, because redox homeostasis is relevant to a wide-range of diseases, this proposal is expected to maximize returns in many other investments of the NIH.
非常需要用于磁共振成像(MRI)的造影剂,其响应于MRI的变化。 氧化还原环境,使新疗法的反应,以指导癌症治疗, 选择,以成像早期反应,推动治疗开发,并使假设测试成为可能 与氧化还原环境和人类健康之间的集体基本理解有关。很长的- 该研究项目的长期目标是开发用于MRI的阳性造影剂,以填补诊断方面的空白 通过专注于含EuII的复合物,这是最有前途的研究领域之一。的 本申请的总体目标是建立必要的基础,为翻译新的欧盟为基础的 通过组装和筛选EuII-和EuII-的库,将复合物转化为有用的氧化还原响应性造影剂 EuIII的配合物的热力学稳定性,动力学惰性,和弛豫。的基本原理 支持拟议的研究是,EuII可以稳定抗氧化,并在体内无毒 通过配体修饰,如最近所证明的,理想的配体系统将协调EuII和 EuIII;并且结合两种氧化态的配体可以用通过以下获得的信息合理地设计: 研究一个复合物库这项建议的预期结果是大大加强 用作造影剂的氧化还原响应性Eu基复合物的化学基础 核磁共振成像。这一结果预计将产生积极的影响,有助于国家卫生研究院的使命, 人类疾病的诊断和新疗法的开发。该提案的目标预计是 通过追求三个具体目标来实现:(1)组装由合成的配体组成的配体库, 穴状配体和市售的非穴状配体;(2)用EuII和GdIII筛选T1- 指示复合物形成的缩短;以及(3)表征热力学稳定性、动力学稳定性和热稳定性。 惰性和弛豫的EuII-和EuIII-含有配合物。新的基于欧盟的探测器将具有重要意义 因为预期它们能够使由治疗引起的氧化还原环境的变化成像, 因此,有助于治疗的开发和选择,并增加对 氧化还原稳态与人体健康的关系。此外,由于氧化还原稳态是 这一建议与广泛的疾病有关,预计将使许多其他投资的回报最大化。 国家卫生研究院

项目成果

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MATTHEW J ALLEN其他文献

MATTHEW J ALLEN的其他文献

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{{ truncateString('MATTHEW J ALLEN', 18)}}的其他基金

MARC at Wayne State University
韦恩州立大学 MARC
  • 批准号:
    10408118
  • 财政年份:
    2021
  • 资助金额:
    $ 31.56万
  • 项目类别:
MARC at Wayne State University
韦恩州立大学 MARC
  • 批准号:
    10620738
  • 财政年份:
    2021
  • 资助金额:
    $ 31.56万
  • 项目类别:
Library Synthesis and Screening of Eu(II)-Based Contrast Agents
基于 Eu(II) 的造影剂的文库合成和筛选
  • 批准号:
    10377906
  • 财政年份:
    2019
  • 资助金额:
    $ 31.56万
  • 项目类别:
Library Synthesis and Screening of Eu(II)-Based Contrast Agents
基于 Eu(II) 的造影剂的文库合成和筛选
  • 批准号:
    10330634
  • 财政年份:
    2019
  • 资助金额:
    $ 31.56万
  • 项目类别:
Intratumoral imaging of hypoxia using 1H- and 19F-MRI with redox-responsive Eu-based contrast agents
使用 1H 和 19F-MRI 以及氧化还原响应铕对比剂进行肿瘤内缺氧成像
  • 批准号:
    10239104
  • 财政年份:
    2018
  • 资助金额:
    $ 31.56万
  • 项目类别:
Study of Advanced Eu(II)-Based Contrast Agents for Ultra-High Field Magnetic Reso
先进Eu(II)基超高场磁共振造影剂的研究
  • 批准号:
    8628271
  • 财政年份:
    2014
  • 资助金额:
    $ 31.56万
  • 项目类别:
Study of Advanced Eu(II)-Based Contrast Agents for Ultra-High Field Magnetic Reso
先进Eu(II)基超高场磁共振造影剂的研究
  • 批准号:
    9059260
  • 财政年份:
    2014
  • 资助金额:
    $ 31.56万
  • 项目类别:
Study of Advanced Eu(II)-Based Contrast Agents for Ultra-High Field Magnetic Reso
先进Eu(II)基超高场磁共振造影剂的研究
  • 批准号:
    9043062
  • 财政年份:
    2014
  • 资助金额:
    $ 31.56万
  • 项目类别:
Study of Advanced Eu(II)-Based Contrast Agents for Ultra-High Field Magnetic Reso
先进Eu(II)基超高场磁共振造影剂的研究
  • 批准号:
    8806558
  • 财政年份:
    2014
  • 资助金额:
    $ 31.56万
  • 项目类别:
Increasing the Utility of Contrast Agents for MRI
提高 MRI 造影剂的实用性
  • 批准号:
    7753605
  • 财政年份:
    2008
  • 资助金额:
    $ 31.56万
  • 项目类别:

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以额叶功能为中心的汽车驾驶能力评价方法的建立及其在事故预测中的应用
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