Visualizing oxidative stress using hyperpolarized magnetic resonance
使用超极化磁共振可视化氧化应激
基本信息
- 批准号:10612868
- 负责人:
- 金额:$ 64.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAddressAgingAnimal ModelAntioxidantsAscorbic AcidBiochemical ReactionBiomedical EngineeringBlood - brain barrier anatomyBrainBrain NeoplasmsCancer BiologyCell DeathCellsCellular StressChemicalsChemotherapy and/or radiationClinicalDNA DamageDataDetectionDevelopmentDiseaseDoseEnvironmentEquilibriumFaceFeasibility StudiesFoundationsFutureGenerationsGlycolysisGoalsHomeostasisHumanImageImaging technologyIn VitroIsotopesLearningLiquid substanceMagnetic ResonanceMagnetic Resonance ImagingMalignant NeoplasmsMeasurementMeasuresMetabolicMetabolic PathwayMetabolismMethodsMolecular ProbesMonitorMotivationMusNerve DegenerationNeurodegenerative DisordersOxidantsOxidation-ReductionOxidative StressPathogenesisPathologyPatientsPhysical ChemistryPlayPre-Clinical ModelProcessPyruvateRadiationRadiation therapyReactive Oxygen SpeciesRelaxationResearchResearch ProposalsRoleSignal TransductionSignaling MoleculeSolidSystemTherapeuticTimeTissuesToxicologyTranslatingTranslationsTransport ProcessVisualizationWorkascorbateblood-brain barrier crossingbrain tumor imagingcancer therapyclinical translationdehydroascorbatedesigndocosahexaenoylascorbic acidexperiencefirst-in-humanhuman imagingimaging approachimaging modalityin vivoindividualized medicineinnovationmetabolic abnormality assessmentmetabolic imagingmolecular imagingmouse modelnon-invasive imagingnon-invasive monitornovelnovel strategiesoxidationpreclinical studysmall moleculespectroscopic imagingstandard of caretranslation to humanstreatment planningtreatment response
项目摘要
PROJECT SUMMARY/ABSTRACT
Reactive oxygen species (ROS) are the byproduct of normal metabolism as well as the differential state and
environment of the cell. They lead to oxidative stress and can be the causes of multiple pathologies, including
cancer. Moreover, oxidative stress and the cell's ability to deal with it can play a major role in the treatment of
these diseases. However, current methods to quantify oxidative stress in vivo are severely lacking and to date
there is no routine method to non-invasively image redox or oxidative stress in humans.
A new platform, hyperpolarized MRI, has the potential to change the way we interrogate metabolism in vivo. We
and others have utilized the power of this approach, combined with endogenous substrates, to non-invasively
image a metabolic substrate and its subsequent downstream products using conventional MRI. In our preliminary
work, we have developed a novel approach to imaging oxidative stress using HP dehydroascorbate (HP DHA),
the oxidized form of vitamin C. Using HP DHA, we are able to image the in vivo generation of HP vitamin C and
utilize the cells' endogenous system to create a non-invasive redox measurement. Combining this with fast
spectroscopic imaging approaches provides a means of readily imaging redox in mice.
These exciting developments provide the basis for pursuing the objectives of this innovative proposal to utilize HP
DHA MRI to further quantify oxidative stress in vivo. Using HP DHA, we will develop a parameter for conversion to
Vitamin C in vivo that quantifies the amount of oxidative stress the cell is under using both acute generation of
ROS in the normal brain and models of murine brain tumors treated with radiation. In parallel, we will utilize what
we have recently learned about the physical chemistry of hyperpolarized probes to design a more robust and
better performing HP DHA. Finally, we will conduct the optimization and toxicology studies necessary to translate
HP DHA to humans, aiming to conduct the first-in-human studies of this approach.
It is the overarching goal of this proposal to use this novel approach in metabolic imaging and lay the foundation
for future metabolic imaging of oxidative stress in patients. This effort will also provide a means of non-invasively
monitoring treatment response that aims to increase oxidative stress, which could be readily integrated into
standard MRI.
项目摘要/摘要
活性氧物种(ROS)是正常代谢的副产品,也是差异状态和
细胞的环境。它们会导致氧化应激,并可能是多种病理的原因,包括
癌症。此外,氧化应激和细胞的处理能力在治疗糖尿病的过程中发挥着重要作用。
这些疾病。然而,目前严重缺乏对体内氧化应激进行量化的方法,而且到目前为止
没有常规的方法来非侵入性地成像人类的氧化还原或氧化应激。
一种新的平台,超极化核磁共振,有可能改变我们在体内询问新陈代谢的方式。我们
还有一些人利用这种方法的力量,结合内源底物,以非侵入性的方式
使用常规核磁共振成像代谢底物及其后续的下游产品。在我们的预赛中
工作中,我们开发了一种使用HP脱氢抗坏血酸(HP DHA)对氧化应激进行成像的新方法,
维生素C的氧化形式使用HP DHA,我们能够成像体内HP维生素C和
利用细胞的内源性系统来创造一种非侵入性的氧化还原测量。将其与FAST结合使用
光谱成像方法提供了一种在小鼠身上容易成像的氧化还原方法。
这些令人振奋的发展为实现这一利用惠普的创新计划的目标奠定了基础
DHA MRI以进一步量化体内的氧化应激。使用HP DHA,我们将开发一个参数以转换为
体内的维生素C,它量化了细胞所处的氧化应激量,使用两种急性生成的
正常大脑和放射治疗的小鼠脑瘤模型中的ROS。同时,我们将利用
我们最近了解了超极化探测器的物理化学,以设计出更强大和
更好地执行HP DHA。最后,我们将进行翻译所需的优化和毒理学研究
惠普DHA给人类,目标是进行这种方法的第一次人体研究。
这项提议的首要目标是将这一新方法应用于代谢成像并奠定基础
用于未来患者氧化应激的代谢成像。这一努力还将提供一种非侵入性的手段
监测旨在增加氧化应激的治疗反应,这可以很容易地整合到
标准核磁共振。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
High Fructose Drives the Serine Synthesis Pathway in Acute Myeloid Leukemic Cells.
- DOI:10.1016/j.cmet.2020.12.005
- 发表时间:2021-01-05
- 期刊:
- 影响因子:29
- 作者:Jeong S;Savino AM;Chirayil R;Barin E;Cheng Y;Park SM;Schurer A;Mullarky E;Cantley LC;Kharas MG;Keshari KR
- 通讯作者:Keshari KR
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Kayvan R Keshari其他文献
Kayvan R Keshari的其他文献
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{{ truncateString('Kayvan R Keshari', 18)}}的其他基金
Interrogation of the oxidative-stress-induced leukemia program in vivo using metabolic imaging
使用代谢成像研究体内氧化应激诱导的白血病程序
- 批准号:
10729140 - 财政年份:2023
- 资助金额:
$ 64.67万 - 项目类别:
Image-guided Trp-IDO/TDO-Kyn-AHR pathway inhibition, combined with immunotherapy
图像引导 Trp-IDO/TDO-Kyn-AHR 通路抑制结合免疫治疗
- 批准号:
10600027 - 财政年份:2021
- 资助金额:
$ 64.67万 - 项目类别:
Image-guided Trp-IDO/TDO-Kyn-AHR pathway inhibition, combined with immunotherapy
图像引导 Trp-IDO/TDO-Kyn-AHR 通路抑制结合免疫治疗
- 批准号:
10721993 - 财政年份:2021
- 资助金额:
$ 64.67万 - 项目类别:
Leveraging fructose transport to create a privileged substrate to selectively fuel T cells
利用果糖运输创造一种特殊底物来选择性地为 T 细胞提供燃料
- 批准号:
10529307 - 财政年份:2020
- 资助金额:
$ 64.67万 - 项目类别:
Visualizing oxidative stress using hyperpolarized magnetic resonance
使用超极化磁共振可视化氧化应激
- 批准号:
10037873 - 财政年份:2020
- 资助金额:
$ 64.67万 - 项目类别:
Leveraging fructose transport to create a privileged substrate to selectively fuel T cells
利用果糖运输创造一种特殊底物来选择性地为 T 细胞提供燃料
- 批准号:
10318220 - 财政年份:2020
- 资助金额:
$ 64.67万 - 项目类别:
Visualizing oxidative stress using hyperpolarized magnetic resonance
使用超极化磁共振可视化氧化应激
- 批准号:
10402394 - 财政年份:2020
- 资助金额:
$ 64.67万 - 项目类别:
Visualizing oxidative stress using hyperpolarized magnetic resonance
使用超极化磁共振可视化氧化应激
- 批准号:
10162569 - 财政年份:2020
- 资助金额:
$ 64.67万 - 项目类别:
Human Tissue Culture Bioreactor and Hyperpolarized MR for Biomarker Discovery
用于生物标志物发现的人体组织培养生物反应器和超极化 MR
- 批准号:
8691806 - 财政年份:2013
- 资助金额:
$ 64.67万 - 项目类别:
Human Tissue Culture Bioreactor and Hyperpolarized MR for Biomarker Discovery
用于生物标志物发现的人体组织培养生物反应器和超极化 MR
- 批准号:
8670990 - 财政年份:2013
- 资助金额:
$ 64.67万 - 项目类别:
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