Dual function pH and oxygen probes for in vivo EPR spectroscopy and imaging

用于体内 EPR 光谱和成像的双功能 pH 和氧探头

基本信息

  • 批准号:
    7686198
  • 负责人:
  • 金额:
    $ 22.5万
  • 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:
    2008-09-15 至 2010-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this project is to develop new probes of enhanced functionality and stability for in vivo EPR spectroscopy and imaging. Functionally oriented classes of soluble paramagnetic probes such as pH, SH- and NO-sensitive nitroxyl radicals (NR) have been developed but they often suffer from insufficient stability in living tissues. In turn, triarylmethyl (TAM) radicals have been the popular choice for EPR imaging applications offering advantages over nitroxides, that is, stability in cells and tissues, and narrow linewidth, resulting in high analytical resolution at 5M concentrations and enhanced sensitivity to O2. However, until now applications of TAM radicals have been functionally limited, mostly to EPR oximetry. In this project we propose to enhance the functionality of TAM radicals by developing pH sensitive derivatives in addition to oxygen sensing. Taking into account that both oxygen and pH play key roles in cellular metabolism and homeostasis, these probes may become useful tools in biomedical research. The specific aims are: (SA1) to synthesize pH-sensitive trityl radicals. The synthetic route for the incorporation of specific ionizable groups, which provide pH sensitivity to TAM derivatives in the desirable pH range, is proposed. The probes synthesized under the SA1 are the basis for the entire project. (SA2) To define the spectroscopic and physico-chemical characteristics of pH- and O2-sensitive TAMs. Quantitative characterization of the newly synthesized TAMs is absolutely crucial, both for the optimization of the synthetic procedure (i.e. the choice of the most effective probes) and for the efficiency of their further spectroscopic and imaging applications. (SA3) To study the role of myocardial acidosis and oxygen depletion in ischemic hearts and in the model of ischemic preconditioning using newly developed TAMs. The measurement of pH and oxygen depletion in ischemic heart is of principal importance for understanding related biochemical processes believed to contribute to myocardial injury, and will be measured in controlled and preconditioned rat hearts using developed extremely stable probes of dual functionality. The results will contribute to the understanding of preconditioning mechanisms and provide opportunities for designing corresponding therapeutic approaches. In summary, the success of this project may have a significant impact on the future of in vivo EPR spectroscopy and bioimaging applications to medicine.
描述(由申请人提供):本项目的总体目标是开发用于体内EPR光谱和成像的增强功能和稳定性的新探针。已经开发了功能导向类的可溶性顺磁性探针,例如pH、SH-和NO-敏感的硝酰基自由基(NR),但是它们通常在活组织中稳定性不足。反过来,三芳基甲基(TAM)自由基已成为EPR成像应用的热门选择,提供了优于氮氧化物的优势,即在细胞和组织中的稳定性,以及窄线宽,导致在5 M浓度下的高分析分辨率和对O2的灵敏度增强。然而,到目前为止,TAM自由基的应用在功能上受到限制,主要是EPR血氧测定。在这个项目中,我们建议通过开发除了氧传感之外的pH敏感衍生物来增强TAM自由基的功能。考虑到氧气和pH在细胞代谢和稳态中起着关键作用,这些探针可能成为生物医学研究中有用的工具。具体目标是:(SA 1)合成pH敏感的三苯甲基自由基。提出了将特定的可电离基团引入的合成路线,所述可电离基团在所需的pH范围内提供对TAM衍生物的pH敏感性。根据SA 1合成的探针是整个项目的基础。(SA2)确定pH和O2敏感TAM的光谱和理化特性。新合成的TAM的定量表征对于合成过程的优化(即最有效探针的选择)以及它们进一步光谱和成像应用的效率都是绝对关键的。(SA3)研究心肌酸中毒和氧耗在缺血心脏中的作用,以及在使用新开发的TAM的缺血预处理模型中的作用。缺血性心脏的pH值和氧耗的测量是最重要的了解相关的生化过程,认为有助于心肌损伤,并将在控制和预处理的大鼠心脏使用开发的非常稳定的双功能探针进行测量。这一结果将有助于理解预适应机制,并为设计相应的治疗方法提供机会。总之,该项目的成功可能对体内EPR光谱和医学生物成像应用的未来产生重大影响。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Valery V Khramtsov其他文献

Functional EPR Spectroscopy of Isolated Perfused Rat Heart: Measurements of Tissue Oxygenation, pH and Glutathione Concentration
  • DOI:
    10.1016/j.freeradbiomed.2010.10.036
  • 发表时间:
    2010-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Denis A Komarov;Valery V Khramtsov
  • 通讯作者:
    Valery V Khramtsov
Special issue for the International Conference on Electron Special issue for the International Conference on Electron Paramagnetic Resonance Spectroscopy and Imaging of Biological Paramagnetic Resonance Spectroscopy and Imaging of Biological Systems (EPR-2017) Systems (EPR-2017)
国际电子会议特刊 电子顺磁共振波谱学和生物系统成像国际会议特刊 (EPR-2017) 系统 (EPR-2017)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Valery V Khramtsov;Michael Jonathan Davies
  • 通讯作者:
    Michael Jonathan Davies
Discriminating Detection of NO and HNO using Encapsulated Nitronyl Nitroxides
  • DOI:
    10.1016/j.freeradbiomed.2010.10.290
  • 发表时间:
    2010-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Andrey A Bobko;Alexander Ivanov;Valery V Khramtsov
  • 通讯作者:
    Valery V Khramtsov
154 - Extracellular Phosphate as a Marker for Tumor Growth
  • DOI:
    10.1016/j.freeradbiomed.2015.10.195
  • 发表时间:
    2015-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    Andrey A Bobko;Timothy D Eubank;Mikhail A Gavrilin;Yakov Y Woldman;Valery V Khramtsov
  • 通讯作者:
    Valery V Khramtsov
283 - Multifunctional Assessment of Tissue <em>p</em>O2, PH and Inorganic Phosphate (Pi) Using <em>in Vivo</em> EPR and Phosphanated Trityl Probe: Interstitial Pi as a New Prognostic Factor in Tumorigenesis
  • DOI:
    10.1016/j.freeradbiomed.2014.10.180
  • 发表时间:
    2014-11-01
  • 期刊:
  • 影响因子:
  • 作者:
    Andrey A Bobko;Timothy D Eubank;Ilirian Dhimitruka;Jay L Zweier;Valery V Khramtsov
  • 通讯作者:
    Valery V Khramtsov

Valery V Khramtsov的其他文献

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{{ truncateString('Valery V Khramtsov', 18)}}的其他基金

Profiling chemical tumor microenvironment: application for diagnostics & therapy
分析肿瘤化学微环境:诊断应用
  • 批准号:
    9749962
  • 财政年份:
    2015
  • 资助金额:
    $ 22.5万
  • 项目类别:
Profiling chemical tumor microenvironment: Application for diagnostics & therapy
分析肿瘤化学微环境:诊断应用
  • 批准号:
    9981151
  • 财政年份:
    2015
  • 资助金额:
    $ 22.5万
  • 项目类别:
Profiling chemical tumor microenvironment: application for diagnostics & therapy
分析肿瘤化学微环境:诊断应用
  • 批准号:
    9115556
  • 财政年份:
    2015
  • 资助金额:
    $ 22.5万
  • 项目类别:
Profiling chemical tumor microenvironment: application for diagnostics & therapy
分析肿瘤化学微环境:诊断应用
  • 批准号:
    9172930
  • 财政年份:
    2015
  • 资助金额:
    $ 22.5万
  • 项目类别:
Profiling chemical tumor microenvironment: application for diagnostics & therapy
分析肿瘤化学微环境:诊断应用
  • 批准号:
    9318478
  • 财政年份:
    2015
  • 资助金额:
    $ 22.5万
  • 项目类别:
Functional proton-electron double-resonance imaging: development and application
功能性质子电子双共振成像:开发与应用
  • 批准号:
    8458951
  • 财政年份:
    2012
  • 资助金额:
    $ 22.5万
  • 项目类别:
Functional proton-electron double-resonance imaging: development and application
功能性质子电子双共振成像:开发与应用
  • 批准号:
    8645629
  • 财政年份:
    2012
  • 资助金额:
    $ 22.5万
  • 项目类别:
Functional proton-electron double-resonance imaging: development and application
功能性质子电子双共振成像:开发与应用
  • 批准号:
    8305365
  • 财政年份:
    2012
  • 资助金额:
    $ 22.5万
  • 项目类别:
NanoSPINs for In Vivo EPR-Based Spectroscopy and Imaging
用于基于 EPR 的体内光谱和成像的 NanoSPIN
  • 批准号:
    7923988
  • 财政年份:
    2009
  • 资助金额:
    $ 22.5万
  • 项目类别:
Functional Proton Electron Double Resonance Imaging
功能质子电子双共振成像
  • 批准号:
    7642583
  • 财政年份:
    2009
  • 资助金额:
    $ 22.5万
  • 项目类别:

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