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

• 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
• 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

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 在过去的几年里，人们对放射性核素化学研究的紧迫感和新的兴趣， 生物学已经出现，因为核恐怖主义的威胁变得更加可信，因为研究医学 工具寻求放射性核素的放射性特性，并作为环境污染的风险 人体暴露于放射性同位素的量也随之增加。在这个项目中，我们将继续分析 将宏观尺度以外的放射性核素分布纳入中、微观和纳米尺度， 剂量学建模和生物学分析，符合生物学终点，从而使有意义的 在内部发射体暴露的背景下制定对策。辐射损害和健康风险 由内化的放射性核素呈现的放射性可以通过使用缓解剂，例如去钙剂， 减少内部污染。然而，大多数有效的药剂仅增强有限的 一系列放射性核素，有些是制定的方式，使管理在大规模伤亡 挑战性的情况。因此，开发改进的脱钙疗法和更好的输送 螯合剂系统是放射性和核威胁对策领域的一个优先研究项目。这 该项目专门针对迫切需要开发和实施放射性同位素的改进疗法 大量人口的污染。它将在成年和幼年动物模型中建立生物动力学特征， 暴露生物标志物的发现，并将新的治疗性脱钙剂的适应症扩展到 选择吸入颗粒形式的放射性同位素，通过证明这种放射性同位素的暴露后效力， 预防长期肺部沉积和随后的损害。此外，通过将不同的 辐射毒性生物标志物对辐射防护效果的影响，本研究将为辐射防护提供基础数据 需要确定治疗的必要性、疗程和终点。