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和核素的研究产生了紧迫感和新的兴趣 随着核恐怖主义的威胁变得更加可信，生物学已经出现，因为调查医学 工具已经寻求放射性核素的放射性特性，并将其视为环境污染的风险 因此，人类接触放射性同位素的量也增加了。在这个项目中，我们将继续分析 放射性核素分布超越宏观，进入中、微和纳米尺度，以改善 剂量学建模和生物动力学分析，符合生物终点，从而使有意义的 在发射器内部暴露的背景下的对策发展。辐射损害和健康风险 由内在化的放射性核素提供的可通过使用诸如脱孔剂的缓释剂来缓解， 减少内部污染。然而，大多数有效的药物只能增强有限的消除 一系列放射性核素，其中一些的配方会导致大量人员伤亡 具有挑战性的情况。因此，改进的去孔洞疗法的发展和更好的交付 用于螯合剂的系统是辐射和核威胁对策领域的研究重点。这 该项目具体解决了开发和实施改进的放射性同位素疗法的迫切需要。 对大量人口的污染。它将在成年和幼年动物模型中建立生物动力学模型，使 暴露的生物标志物的发现，并将一种新的治疗性脱孔剂的适应症扩展到 以吸入颗粒物的形式选定的放射性同位素，通过展示这一物质暴露后的效力 该产品用于防止长期的肺沉积和随后的损害。此外，通过将不同的 辐射毒性生物标志物对对策疗效的影响，为本研究提供基础数据 需要确定治疗的需要、疗程和终点。