Project 3: Elemental Microscopy for Detection of Radionuclide Distribution and Development of Cell and Tissue Phantoms

项目 3：用于检测放射性核素分布和细胞和组织模型开发的元素显微镜

基本信息

批准号：
10589884
负责人：
GAYLE E. WOLOSCHAK
金额：
$ 40.66万
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/10589884
关键词：
3-Dimensional Accidents Acute Address Affect Animal Model Animals Archives Back Biological Biological Markers Canis familiaris Cell Death Cell Lineage Cells Cellular biology Chemicals Chemistry Complex DNA Damage Data Daughter Deposition Detection Development Devices Dimensions Discipline of Nuclear Medicine Distant Elements Evaluation Exposure to External Beam Radiation Therapy Fibrosis Fluorescence Fluorescence Microscopy Generations Genotype Goals Half-Life Health Heterogeneity Histologic Histology Image Immune system Immunohistochemistry Immunology Inhalation Intake Left Life Link Liver Location Lung Lymphocyte Lymphoid Cell Macrophage Maps Messenger RNA MicroRNAs Microscopy Modeling Molecular Molecular Biology Morphology Motivation Mus Myeloid Cells Nature Normal tissue morphology Nuclear Nuclear Reactor Accidents Organ Organism Outcome Particle Size Particulate Pattern Periodicals Phenotype Positioning Attribute Production Property Radiation Radiation Protection Radiation induced damage Radiobiology Radioisotopes Radiology Specialty Recovery Research Resources Roentgen Rays Route Sampling Selection Criteria Signal Transduction Slide Solubility Source Spleen Technology Tissue Sample Tissues Tomogram Toxic effect Universities Vertebral column Visible Radiation animal tissue biomarker discovery biomarker evaluation biomarker identification cell injury chemokine cytokine density dosimetry efficacy evaluation grasp immune cell infiltrate improved in vivo insight internal radiation intravenous injection light microscopy microscopic imaging morphometry nanoscale radiation mitigation radiochemical response sample archive senescence stem submicron synergism tissue phantom tool

项目摘要

PROJECT 3: ABSTRACT The overall objective of Project 3 is to link radionuclide exposure and the elemental signature left behind with biomarkers of that exposure, be they histological, cellular or molecular in nature. Our motivation to do this stems from the fact that radiation from internal emitters is very unevenly distributed in organs, tissues, and cells and the fact that this remains little understood. Heterogeneity of radionuclide distribution is dependent upon a complex set of parameters that relate to the radionuclide itself and the organism’s response to it, such as radionuclide half-life, decay schema, activity, concentration, particle size, morphology, chemical form, and solubility, whereas the biological response patterns are dictated by the genotype and phenotype of the cells, tissues and organs, intake route and the organism as a whole. Because the in vivo footprint of radionuclide exposure is multi-scale, e.g., DNA damage and cell death at the (sub)cellular level, or chemokine/cytokine production at the cell/tissue level, it essentially means that biomarkers of that exposure are best registered along the same multi-dimensional NANO-, MICRO- and MESO scale, which is our goal. For example, micro-RNA expression will be registered in the context of immune cell infiltration in a tissue, particularly macrophages. Arguably, the most compelling aspect to our project can be seen in the use of X-ray fluorescent microscopy (XFM) as a powerful tool for radionuclide mapping, which forms the backbone to our approach. Applying XFM technology to explore the incredibly rich resource that the Northwestern University Radiation Animal (NURA) Archive, combined with contemporary animal models gives us the unique opportunity to trace back the biological consequences of radionuclide exposures, and opens up the path towards biomarker, and ultimately, to mitigator discovery. Canine and murine tissues from an enormous number of animals exposed to a variety of radionuclides and over different times add critical mass and rigor to our study. Collectively, our team can draw from a diverse set of expertise in nuclear medicine, cellular and molecular biology, radiobiology, XFM, radiation protection and mitigation, normal tissue radiobiology and immunology. We are ideally placed to carry out the proposed studies addressing the complexity of radionuclide exposure in a comprehensive and integrated way. Our hope is to gain important insights into the biological consequences of internal radiation emitters that are relevant to real life accidental and incidental exposure scenarios and that cannot be modeled using conventional external beam radiation or nuclear medicine approaches. Yet, the concepts underlying the interaction between radiation-damaged cells and tissues, danger signaling, the engagement of immune system and the road to recovery are likely applicable in a much broader context.

项目 3：摘要项目 3 的总体目标是将放射性核素暴露与留下的元素特征联系起来这种暴露的生物标志物，无论是组织学的、细胞的还是分子的，都是我们这样做的动机。来自内部发射器的辐射在器官、组织和细胞中的分布非常不均匀，事实上，这一点仍然知之甚少，放射性核素分布的异质性取决于一个。与放射性核素本身以及生物体对其响应相关的一组复杂参数，例如放射性核素半衰期、衰变模式、活度、浓度、颗粒大小、形态、化学形态，以及溶解度，而生物反应模式由细胞的基因型和表型决定，组织和器官、摄入途径和整个生物体。因为放射性核素暴露的体内足迹是多尺度的，例如，DNA损伤和细胞死亡（亚）细胞水平，或细胞/组织水平的趋化因子/细胞因子的产生，本质上意味着生物标志物该暴露的最好记录在相同的多维纳米、微米和中观尺度上，这是我们的目标，例如，微RNA表达将在免疫细胞浸润的背景下被记录。组织，特别是巨噬细胞，可以说，我们的项目最引人注目的方面是使用 X 射线荧光显微镜 (XFM) 作为放射性核素图谱的强大工具，构成了放射性核素图谱分析的支柱我们的方法应用 XFM 技术来探索西北大学极其丰富的资源。辐射动物（NURA）档案与当代动物模型相结合为我们提供了独特的机会追溯放射性核素暴露的生物学后果，并开辟通往生物标志物的道路，最终，从大量暴露的动物中发现了缓解剂。对各种放射性核素和不同时间的研究增加了我们研究的临界质量和严谨性。总的来说，我们的团队可以借鉴核医学、细胞和分子领域的各种专业知识生物学、放射生物学、XFM、辐射防护和缓解、正常组织放射生物学和免疫学。非常适合开展拟议的研究，解决放射性核素暴露的复杂性我们希望以全面、综合的方式获得对生物学后果的重要见解。与现实生活中的意外和暴露场景相关的内部入射辐射发射器然而，无法使用传统的外束辐射或核医学方法进行建模。辐射损伤细胞和组织之间相互作用的概念、危险信号、免疫系统的参与和康复之路可能适用于更广泛的背景。