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
- 来源:
- 关键词:AreaAutomobile DrivingBindingChemicalsChemistryClinicalComplexContrast MediaDataDevelopmentDiagnosisDiagnosticDiseaseEnsureEnvironmentEuropiumExhibitsFoundationsFutureGlutathioneGoalsHealthHomeostasisHumanHuman DevelopmentHypoxiaImageInvestmentsIonsKineticsKnowledgeLibrariesLigand BindingLigandsMagnetic Resonance ImagingMalignant NeoplasmsMeasuresMedicalMedicineMetalsMissionModificationMonitorNecrosisOutcomeOxidantsOxidation-ReductionOxidesPrecipitationPropertyPublic HealthRapid screeningResearchResearch Project GrantsS PhaseSelection for TreatmentsSolidStructureSystemTestingThermodynamicsTissue DifferentiationTranslationsTumor TissueUnited States National Institutes of Healthbasecancer diagnosiscancer therapycontrast enhanceddesignexperimental studyhuman diseaseimprovedin vivoinnovationinterestnovel therapeuticsoxidationpreclinical studyresponsescreeningsmall moleculetherapy developmenttherapy outcometooltrendtumortumor hypoxia
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.
磁共振成像(MRI)对造影剂的需求很大,因为它能对血管的变化做出反应
项目成果
期刊论文数量(0)
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MATTHEW J ALLEN的其他文献
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{{ truncateString('MATTHEW J ALLEN', 18)}}的其他基金
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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