Imaging Biomarkers of Neurotoxicity in Welders

焊工神经毒性的成像生物标志物

基本信息

批准号：
8593295
负责人：
Brad A Racette
金额：
$ 58.51万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-12-06 至 2017-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8593295
关键词：
Adult Affect Age Air Basal Ganglia Binding Biological Markers Brain Brain region Carboxy-Lyases Child Chronic Clinical assessments Communities Corpus striatum structure Data Dopa Dopamine Dopamine D2 Receptor Dose Environment Environmental Health Epidemiology Exposure to Financial compensation Functional disorder Funding Future Gender Goals Grant Hazardous Substances Health Health Hazards High Prevalence Human Image Institution Investigation Ligands Magnetic Resonance Imaging Manganese Measures Mediating Metals Methods Molecular National Institute of Environmental Health Sciences Neuraxis Neurologic Neurologic Effect Neurons Neurotoxins Occupational Health Parkinson Disease Parkinsonian Disorders Positron-Emission Tomography Publishing Research Personnel Research Project Grants Role Scanning Soil Synapses System Techniques Time Water Welding base career cohort dihydrotetrabenazine dopamine system dopaminergic neuron imaging modality in vivo molecular imaging neurotoxicity pet animal postsynaptic presynaptic public health relevance putamen radioligand receptor response uptake vesicular monoamine transporter

项目摘要

DESCRIPTION (provided by applicant): Manganese (Mn) is a neurotoxicant that is present in soil, air, and water. Investigations of occupationally- exposed groups, such as welders, provide an ideal opportunity to characterize dose-related dopaminergic system damage associated with Mn. Recent studies from our collaborating institutions demonstrate a high prevalence of Parkinsonism in workers with chronic exposure to Mn containing welding fumes and dopaminergic dysfunction on [18F] fluorodopa (FDOPA) PET. This study utilizes an established, well characterized cohort of welders with detailed exposure and clinical assessments, developed through NIEHS funded research projects. For this proposal, a cohort of 40 career welders with baseline FDOPA PET scans will undergo repeat PET imaging of the nigrostriatal dopamine system using FDOPA and first time imaging with the presynaptic dopaminergic radioligand [11C]dihydrotetrabenazine (DTBZ) and the post-synaptic dopamine D2 receptor selective radioligand [11C]N-methylbenperidol (NMB). These workers will be compared to a second group of non-welder reference subjects who will be imaged at baseline and four years. The specific goals of this project are: 1) to investigate progression of dopaminergic dysfunction in welding exposed workers as evidence of progressive neurotoxicity, 2) to use the radioligand DTBZ to investigate the dose-response relationship with welding fume exposure as an indicator of the underlying etiologic relationship between Mn and damage to the presynaptic dopaminergic system, and 3) to use the radioligand NMB to investigate the dose-response relationship with welding fume exposure as an indicator of the underlying etiologic relationship between Mn and damage to the postsynaptic dopamine system. This proposal uses state-of-the-art imaging methods to investigate the health effects of a common environmental and occupational health hazard. The results of this study will have broad implications for public and worker health worldwide and will inform future community based studies of metal neurotoxicity. In addition, this study, in conjunction with our previously published data, will provide converging evidence of the role of Mn as a nigrostriatal neurotoxin. The methods described in this application represent cutting edge molecular and MRI techniques and the institutions and investigators are ideally suited for this unique epidemiology and imaging proposal.

描述（由申请人提供）：锰（MN）是一种神经毒性，存在于土壤，空气和水中。对焊工等职业暴露群体的调查为表征与MN相关的剂量相关多巴胺能系统损害提供了理想的机会。我们合作机构的最新研究表明，在[18F] Fluorodopa（FDOPA）PET上，长期暴露于MN的工人中，帕金森氏症患病率很高。这项研究利用了通过NIEHS资助的研究项目开发的，具有详细的焊工和临床评估，具有详尽的焊工队列。对于这项建议，使用FDOPA扫描基线的40个职业焊机组成的队列将使用FDOPA对骨纹状体多巴胺进行重复成像，并首次使用突触前多巴胺能放射性辐射[11C] Dihytrototetrotetrotetrotetrotetrotetrotetrigigrig radigiol dtbz和Symiol radiol dopaminiol dopaminiol dopaminic d2 d2 [11C] N-甲基苯甲酰醇（NMB）。这些工人将与第二组非驾驶参考受试者进行比较，他们将在基线和四年内成像。该项目的具体目标是：1）调查多巴胺能功能障碍在焊接暴露的工人中作为进行性神经毒性的证据的进展，2）使用放射性dtbz调查剂量 - 反应关系，以焊接烟雾接触的剂量 - 与下层的损害与3种损坏的损害，并损坏了MN的损害，并损坏了3个损害，以前的损坏了3个）。放射性NMB研究剂量反应与焊接烟雾暴露的关系，作为MN与突触后多巴胺系统损伤之间基本病因的指标。该建议使用最先进的成像方法来研究常见环境和职业健康危害的健康影响。这项研究的结果将对全球公共和工人健康具有广泛的影响，并将为基于社区的金属神经毒性研究提供信息。此外，这项研究以及我们先前发布的数据将提供收敛 MN作为斑纹纹状体神经毒素的作用的证据。本应用中描述的方法代表了尖端分子和MRI技术，并且机构和研究人员非常适合这种独特的流行病学和成像建议。