Rapid Non-invasive Radiation Biodosimetry through Metabolomics

通过代谢组学进行快速无创辐射生物剂量测定

• 批准号: 9753873
• 负责人: Albert J Fornace
• 金额: $ 55.73万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9753873
• 关键词: Address; Affect; Attenuated; Biological; Biological Assay; Biological Markers; Blood specimen; Characteristics; Chest; Chronic; Clinical; Collaborations; Complement; Core Facility; Cytogenetics; Dependence; Development; Devices; Disasters; Disease; Dose; Dose-Rate; Early treatment; Effectiveness; Engineering; Ensure; Event; Experimental Designs; Exposure to; Fast Neutrons; Goals; Guns; Hematopoietic; Human; Image; Immunosuppressive Agents; Individual; Inflammation; Inflammatory; Injury; Investigation; Laboratories; Lethal Dose 50; Lung; Mass Spectrum Analysis; Modeling; Mus; Neutrons; Nuclear; Nuclear Accidents; Nuclear Power Plants; Outcome; Pathway interactions; Pharmaceutical Preparations; Photons; Physiological; Population; Process; Radiation; Radiation Accidents; Radiation Injuries; Radiation Monitoring; Radiation Tolerance; Radiation Toxicity; Radiation exposure; Radiology Specialty; Recovery; Research; Resources; Risk; Sampling; Shipping; Signal Transduction; Source; Standardization; System; Technology; Testing; Therapeutic Intervention; Toxic effect; Treatment Failure; Triage; Uranium; base; benefit sharing; biodosimetry; biosignature; cohesion; diindolylmethane; drug development; drug testing; experimental study; functional genomics; genetic approach; humanized mouse; improved; instrument; interdisciplinary approach; irradiation; lung injury; metabolomics; minimally invasive; mortality; mouse model; programs; radiation mitigator; radiation-induced injury; reconstruction; response; response to injury; sample collection; specific biomarkers; survival prediction; technology development; tissue biomarkers; transcriptomics

Project 3: Rapid Non-invasive Radiation Biodosimetry through Metabolomics. Metabolomics has been established as a non-invasive approach to basic radiation biodosimetry, and has the potential to discriminate specific features of radiation exposure that are relevant to triage. The proposed studies will characterize the metabolomic effects of dose rate (from 0.25 Gy per day to 2 Gy per second), exposure to the internal emitter 137Cs, and the neutron component of improvised nuclear device (IND) radiation to develop radiation biodosimetry more relevant to real-world exposure scenarios. Dose estimates provide only an indication of the average radiation injury expected across a population. It will also be important to develop predictors of individual radiation injury response and outcome. Early metabolomic predictors of mortality due to late lung injury, as well as signatures of lung injury and recovery, will be developed. Related studies will develop early predictors of mitigator effectiveness, since early indication of treatment failure will give the opportunity to try alternate therapy on an individualized basis. Radiation exposure is known to trigger many inflammation-like processes, suggesting that chronic inflammatory or immunosuppressive conditions, which exist within the human population, may have the potential to confound radiation biodosimetric signatures in affected individuals. To begin addressing this possibility, investigation of the impact of inflammatory pathways on radiation metabolomic biomarkers will be undertaken using mouse models. All the research proposed in Project 3 is ultimately directed toward practical implementation for biodosimetry. Mass spectrometry (MS) is now routinely used in major clinical laboratories, but efficient sample collection, processing, and transport will be required to interface with the available clinical instruments. In support of this larger goal, an integrated blood sample collection and processing card system will be developed in collaboration with the Sample Engineering Core to obtain and pre-process blood samples for shipping to an MS facility. The metabolomic studies proposed in this project will be complemented by investigations of cytogenetic endpoints (Project 1) and transcriptomic profiling (Project 2) and will benefit from shared biological samples and experimental designs. The program Cores will further enhance the planned research by centralizing and standardizing routine functions, such as mouse handling and irradiations, and by providing unique resources, such as the IND-spectrum neutron source and the variable dose rate external 137Cs irradiator (Irradiation Core), and the hematopoietically humanized mouse for biodosimetry (Mouse Core).

项目3：通过代谢组学快速非侵入性辐射生物测量法。代谢组学具有 被确定为基本辐射生物测量法的一种非侵入性方法，并且有潜力 区分与分类有关的辐射暴露的特定特征。拟议的研究将 特征剂量率的代谢组作用（从每天0.25 Gy到每秒2 Gy），暴露于 内部发射极137C，以及即兴核能（IND）辐射的中子成分 辐射生物测量法与现实世界的暴露情况更相关。 剂量估计仅提供了人群预期的平均辐射损伤的指示。它 开发单个辐射损伤反应和结果的预测因素也很重要。早期的 由于肺部后期损伤引起的死亡率以及肺损伤和恢复的签名，代谢组学预测指标将 被开发。相关研究将开发缓解剂有效性的早期预测指标，因为早期迹象表明 治疗失败将有机会在个性化的基础上尝试替代治疗。 已知辐射暴露会触发许多类似炎症的过程，表明慢性 人口中存在的炎症或免疫抑制条件可能具有 在受影响个体中混淆辐射生物测定的潜力。开始解决这个问题 可能性，对炎症途径对辐射代谢组生物标志物的影响的研究将是 使用鼠标模型进行。 项目3中提出的所有研究最终都是针对实施的 生物测量法。现在，质谱法（MS）通常用于主要的临床实验室，但有效样本 收集，处理和运输将被要求与可用的临床仪器接口。在 支持这个更大的目标，将开发集成的血液样本收集和加工卡系统 与样本工程核心合作，以获取和预处理样品，以运送到 女士设施。 该项目中提出的代谢组学研究将由细胞遗传学的研究补充 终点（项目1）和转录组分析（项目2），将受益于共享的生物样品 和实验设计。该计划核心将通过集中化和 标准化常规功能，例如鼠标处理和照射，并通过提供独特的资源， 例如，折射中子源和可变剂量速率外部137C辐照器（辐照核）， 以及造血人性化的小鼠生物测量法（小鼠核）。