Preclinical Electron Paramagnetic Resonance Tumor Imager

临床前电子顺磁共振肿瘤成像仪

• 批准号: 10647895
• 负责人: Gareth R Eaton
• 金额: $ 51万
• 依托单位: UNIVERSITY OF DENVER (COLORADO SEMINARY)
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-08 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10647895
• 关键词: Acute Lung Injury; Acute Respiratory Distress Syndrome; Animals; Biology; Biomedical Research; Biotechnology; Bite; Bleomycin; Blood Vessels; Brain Injuries; Budgets; Chemotherapy and/or radiation; Chicago; Code; Computer software; Data; Development; Disease; Disease Progression; Drug Industry; Electron Spin Resonance Spectroscopy; Engineering; Equilibrium; Evaluation; Feedback; Floor; Free Radicals; Functional disorder; Generations; Glutathione; Goals; Grant; Image; Image Enhancement; Individual; Industrialization; Industry; Inflammation; Inflammatory; Kinetics; Knowledge; Laboratories; Link; Lung diseases; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Mediating; Medical; Medical center; Methods; Mitochondria; Modality; Modeling; Molecular; Monitor; Mus; Myocardial Infarction; Myopathy; Nerve Degeneration; Noise; Oxidation-Reduction; Oxidative Stress; Oxygen; Oxygen saturation measurement; Pathology; Penetration; Performance; Peripheral; Persons; Physiologic pulse; Physiological; Power Sources; Process; Property; Pulse Oximetry; Radiation therapy; Reaction; Reactive Oxygen Species; Relaxation; Reproducibility; Resolution; Respiratory Therapy; Role; Scanning; Severities; Signal Transduction; Source; Specific qualifier value; Spectrum Analysis; Speed; Spin Trapping; Stroke; Students; Superoxides; Surface; System; Techniques; Technology; Testing; Time; Tissues; Training; Trauma; Treatment Efficacy; Tumor Pathology; Universities; Viscosity; Work; Writing; cancer therapy; carcinogenesis; commercialization; data acquisition; design; design and construction; experience; experimental study; frontier; high risk; image reconstruction; imager; imaging modality; improved; in vivo; in vivo imaging; in vivo monitoring; innovation; lung injury; magnetic field; manufacturability; member; microwave electromagnetic radiation; nitroxyl; pre-clinical; preclinical imaging; prototype; reconstruction; software systems; success; targeted cancer therapy; treatment response; tumor; tumor microenvironment; wound healing

Summary Revolutionary methods of acquiring electron paramagnetic resonance (EPR) spectra of free radicals create a paradigm shift in application of EPR to understanding the role of radicals in cancer and in other diseases. Hitherto impossible studies are now feasible. Molecular oxygen, pH, local viscosity, distribution of probes, and general redox status of tissues are crucial parameters to understand tumors, determine targets for radiation and chemotherapy, and to monitor response to treatments. Lung damage, stroke, myocardial infarction, brain injury, wound healing, and other trauma, and peripheral vascular limitations may similarly benefit from EPR imaging of redox status. These physiologic parameters can be measured using nitroxide radicals, which are optimally detected with rapid scan EPR. Pulsed EPR measurement of local oxygen concentration with trityl radicals can guide radiation treatment of tumors in mice. The proposed system will include both of these powerful techniques. Experienced collaborators will test the imager in applications to redox equilibria in mouse tumors, reactive oxygen species related to cancer in mice, and acute lung injury. Space is at a premium in medical facilities, and in industry floor space for a new modality is expensive. Looking toward expanded use in the pharmaceutical industry the 1 GHz imager will be compact and transportable. Smaller, faster, more versatile imaging will enhance applications of oximetric imaging to tumor therapy and to the other pathologies listed above. The prototype with technology for both rapid scan spectroscopy and oximetric imaging will open new vistas for quantifying more physiologic parameters than oximetry alone. The integrated software system will enable use by technicians without advanced training in the underlying spectroscopy. The industrial partner, Bruker BioSpin, and University of Denver’s engineers will design a new generation of 1 GHz cross-loop and surface coil resonators, a small magnet and scan coils. Bruker contributes supplemental (optional) support beyond the grant budget with engineering team commitments to work on commercializing our rapid scan EPR method and components. Bruker brings to the team essential experience and know-how of commercial standards, manufacturability, long-term support, and customer needs. Lack of the proposed capability has stymied the expansion of EPR capabilities into more general biomedical research use. The innovation is the creation of a prototype that our team’s industrial component can refine into a marketable product with powerful EPR capability for end users.

概括 获取自由基电子顺磁共振 (EPR) 谱的革命性方法 应用 EPR 来理解自由基在癌症和其他疾病中的作用，创造了范式转变 疾病。迄今为止不可能的研究现在变得可行。 分子氧、pH、局部粘度、探针分布以及组织的一般氧化还原状态 了解肿瘤、确定放疗和化疗目标以及监测的关键参数 对治疗的反应。肺损伤、中风、心肌梗塞、脑损伤、伤口愈合等 创伤和外周血管限制同样可以受益于氧化还原状态的 EPR 成像。这些 可以使用氮氧自由基来测量生理参数，通过快速扫描可以最佳地检测到氮氧自由基 EPR。用三苯甲基自由基脉冲 EPR 测量局部氧浓度可以指导放射治疗 小鼠肿瘤。拟议的系统将包括这两种强大的技术。经验丰富 合作者将测试成像仪在小鼠肿瘤氧化还原平衡、活性氧中的应用 与小鼠癌症和急性肺损伤有关。 医疗设施中的空间非常宝贵，而在工业中，新模式的占地面积也很昂贵。 为了扩大在制药行业的使用，1 GHz 成像仪将变得紧凑且 可运输。更小、更快、更通用的成像将增强血氧成像在肿瘤中的应用 治疗和上面列出的其他病症。具有快速扫描技术的原型 光谱学和血氧成像将为量化更多的生理参数开辟新的前景 单独进行血氧测定。集成的软件系统将使技术人员无需接受高级培训即可使用 基础光谱学。 工业合作伙伴布鲁克 BioSpin 和丹佛大学的工程师将设计一种新的 生成 1 GHz 交叉环路和表面线圈谐振器、小磁铁和扫描线圈。布鲁克贡献 超出赠款预算的补充（可选）支持，并承诺工程团队致力于开展工作 将我们的快速扫描 EPR 方法和组件商业化。布鲁克为团队带来了重要的经验 以及商业标准、可制造性、长期支持和客户需求方面的专业知识。缺乏 拟议的功能阻碍了 EPR 功能扩展到更一般的生物医学研究 使用。创新是创建一个原型，我们团队的工业组件可以将其细化为 为最终用户提供强大的 EPR 功能的适销产品。

项目成果

Advances in rapid scan EPR spectroscopy.

• DOI: 10.1016/bs.mie.2022.02.013
• 发表时间: 2022
• 期刊: Methods in enzymology

Spin-spin interaction and relaxation in two trityl-nitroxide diradicals.

• DOI: 10.1016/j.jmr.2021.107078
• 发表时间: 2021-11
• 期刊: Journal of magnetic resonance (San Diego, Calif. : 1997)
• 作者: Moore W;Yao R;Liu Y;Eaton SS;Eaton GR
• 通讯作者: Eaton GR

Electron paramagnetic resonance of lanthanides.

• DOI: 10.1016/bs.mie.2021.01.038
• 发表时间: 2021
• 期刊: Methods in enzymology