Project 4: Post-Exposure Biomarkers and Remediation of Radionuclide Contaminants

项目4：暴露后生物标志物和放射性核素污染物的修复

基本信息

批准号：
10589887
负责人：
Rebecca J Abergel
金额：
$ 51.49万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-10 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10589887
关键词：
Accidents Acids Actinoid Series Elements Address Adolescent Animal Model Animals Area Biochemistry Biocompatible Materials Biological Biological Markers Biology Cardiovascular system Cell physiology Chelating Agents Chemicals Chemistry Childhood Complex Data Data Set Dedications Deposition Development Devices Dose Elements Environment Environmental Pollution Environmental Risk Factor Evaluation Event Excision Exposure to Female Gene Expression Gene Expression Alteration Genes Genetic Health Heavy Metals Inhalation Injections Ions Knowledge Laboratories Ligands Literature Lung Medical Meta-Analysis Metals Modeling Molecular Mus Nuclear Nuclear Reactor Accidents Particulate Plutonium Population Property Radiation Radiation Protection Radiation Toxicity Radiation induced damage Radioactive Radioisotopes Radiology Specialty Regulation Research Research Priority Risk Rodent Model Sampling Sex Differences Signal Pathway System Terrorism Therapeutic Toxic effect Toxicology Treatment Efficacy Treatment Protocols Work biomarker discovery chelation comparison control design dosimetry drug development epidemiologic data experimental analysis experimental study exposed human population functional genomics improved in vivo interest juvenile animal male mass casualty mature animal member metal chelator model development nanoscale novel therapeutics particle prevent programs remediation respiratory sample archive sex sex determination specific biomarkers tomography tool transcriptome uptake

Accidents Acids Actinoid Series Elements Address Adolescent Animal Model Animals Area Biochemistry Biocompatible Materials Biological Biological Markers Biology Cardiovascular system Cell physiology Chelating Agents Chemicals Chemistry Childhood Complex Data Data Set Dedications Deposition Development Devices Dose Elements Environment Environmental Pollution Environmental Risk Factor Evaluation Event Excision Exposure to Female Gene Expression Gene Expression Alteration Genes Genetic Health Heavy Metals Inhalation Injections Ions Knowledge Laboratories Ligands Literature Lung Medical Meta-Analysis Metals Modeling Molecular Mus Nuclear Nuclear Reactor Accidents Particulate Plutonium Population Property Radiation Radiation Protection Radiation Toxicity Radiation induced damage Radioactive Radioisotopes Radiology Specialty Regulation Research Research Priority Risk Rodent Model Sampling Sex Differences Signal Pathway System Terrorism Therapeutic Toxic effect Toxicology Treatment Efficacy Treatment Protocols Work biomarker discovery chelation comparison control design dosimetry drug development epidemiologic data experimental analysis experimental study exposed human population functional genomics improved in vivo interest juvenile animal male mass casualty mature animal member metal chelator model development nanoscale novel therapeutics particle prevent programs remediation respiratory sample archive sex sex determination specific biomarkers tomography tool transcriptome uptake

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项目摘要

PROJECT 4: ABSTRACT In the last several years, a sense of urgency and a renewed interest in the study of radionuclide chemistry and biology have emerged, as threats of nuclear terrorism have become more plausible, as investigational medical tools have sought the radioactive properties of radionuclides, and as the risk of environmental contamination and human exposure to radioisotopes consequently increased. In this project, we will pursue the analysis of radionuclide distribution beyond the MACRO into the MESO, MICRO and NANO scales, in order to improve dosimetry modeling and biokinetics analyses, in line with biological endpoints, thereby enabling meaningful countermeasure development in the context of internal emitter exposures. The radiation damage and health risk presented by internalized radionuclides can be mitigated by the use of mitigators, such as decorporation agents, that reduce internal contamination. However, most effective agents enhance the elimination of only a limited range of radionuclides, and some are formulated in ways that would make administration in mass casualty situations challenging. Therefore, the development of improved decorporation therapies and better delivery systems for chelators is a research priority in the area of radiological and nuclear threat countermeasures. This project specifically addresses the urgent need to develop and implement an improved therapy for radioisotope contamination of a large population. It will establish biokinetic profiles in adult and juvenile animal models, enable the discovery of biomarkers of exposure, and extend the indication of a new therapeutic decorporation agent to selected radioisotopes in the form of inhaled particulates, by demonstrating the post-exposure potency of this product at preventing long-term lung deposition and subsequent damage. In addition, by correlating different biomarkers of radiation toxicity to countermeasure’s efficacy, this research will provide the foundational data needed to determine the need for, and course and endpoint of treatment.

项目4：摘要在过去的几年中，对放射性化学研究的研究有一种紧迫感和重新兴趣随着核恐怖主义的威胁变得更加合理，生物学已经出现了工具已寻求放射性的放射性特性，并作为环境污染的风险因此，人类接触放射性同位素。在这个项目中，我们将进行分析为了改善宏观，微观和纳米尺度的宏观分布分布剂量模型和生物动力学分析，与生物学终点一致，从而实现有意义的在内部发射极暴露的背景下，对策开发。辐射损害和健康风险可以通过使用缓解剂（例如装饰剂）来减轻内部放射线的呈现减少内部污染。但是，最有效的代理仅增强了消除有限的消除放射线范围的范围，有些则以使群众伤亡的管理方式制定情况挑战。因此，开发改进的装饰疗法和更好的交付螯合剂系统是放射学和核威胁对策领域的研究重点。这项目专门解决了开发和实施改进的放射性同位素治疗的迫切需求人口众多的污染。它将在成人和少年动物模型中建立生物动力学特征，启用发现暴露的生物标志物，并将新的治疗装饰剂的指示扩展到通过证明这一点的暴露效力，以合并组件的形式进行选定预防长期肺沉积和随后损害的产品。另外，通过关联不同的辐射毒性对对策效率的生物标志物，这项研究将提供基础数据需要确定需要以及治疗的过程和终点。