IMAGING MACROPHAGE ACTIVATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

慢性阻塞性肺疾病中巨噬细胞激活的成像

• 批准号: 8688054
• 负责人: Delphine L Chen
• 金额: $ 37.24万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-25 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8688054
• 关键词: Affect; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Benzodiazepine Receptor; Binding; Bronchoalveolar Lavage; Cells; Chronic Obstructive Airway Disease; Clinical; Clinical Trials; Data; Deoxyglucose; Development; Diagnostic Trial; Dichloromethylene Diphosphonate; Disease; Disease Progression; Excision; Flow Cytometry; GLUT-1 protein; Glucose Transporter; Human; Image; Imaging Techniques; Immune; Immunofluorescence Microscopy; Immunohistochemistry; Immunologic Monitoring; In Situ; Individual; Inflammation; Inflammatory; Interferons; Interleukin-13; Liposomes; Lung; Lung Inflammation; Lung diseases; Macrophage Activation; Measures; Methods; Modeling; Monitor; Monoclonal Antibodies; Morbidity - disease rate; Mus; Neutrophil Activation; Pathogenesis; Patients; Peripheral; Phenotype; Pilot Projects; Positron-Emission Tomography; Proteins; Relative (related person); Research Personnel; Sampling; Sendai virus; Severities; Specificity; Sputum; Staining method; Stains; Structure of parenchyma of lung; Techniques; Testing; Therapeutic Intervention; Time; Tissue Sample; Tissue Stains; Tracer; Transplant Recipients; Tumor Necrosis Factor-alpha; Virus; Virus Diseases; abstracting; cell type; cohort; effective therapy; efficacy testing; fluorodeoxyglucose; glucose uptake; healthy volunteer; in vivo; in vivo imaging; macrophage; methionyl-leucyl-phenylalanine; monocyte; mortality; mouse model; neutrophil; novel; peripheral blood; protein expression; public health relevance; research study; response; tool; treatment response; uptake

DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) is a prevalent inflammatory lung disease for which new tools to quantify lung inflammation are needed to aid the development of effective anti-inflammatory treatments. Macrophage activation is critical to disease progression, so a technique that can track macrophage recruitment and activation in the lungs would be valuable for delineating inflammatory phenotypes in patients with COPD and for assessing anti-inflammatory treatment responses. Positron emission tomography (PET) is a noninvasive technique that can quantify lung inflammation using [18F]fluorodeoxyglucose ([18F]FDG), a commonly used clinical tracer. The novel PET tracer [11C]PBR28 targets the translocator protein (TSPO), which is present at high levels in activated macrophages. This project will test the overall hypothesis that [11C]PBR28 binding and [18F]FDG uptake measured by PET can be used to differentiate macrophage-dominant inflammation from neutrophil-dominant inflammation in patients with COPD. We will accomplish this by first conducting studies of TSPO expression and glucose uptake in ex vivo mouse models of macrophage activation along with microPET imaging and tissue staining to determine the specificity of [11C]PBR28 and [18F]FDG for macrophages and neutrophils in mice following virus infection- induced chronic obstructive lung disease (Aim 1). We will then study TSPO expression and glucose uptake in polarized human peripheral blood monocytes to parallel the mouse experiments and in lung tissue samples donated at the time of transplant by patients with COPD or at the time of lung resection by healthy donors and patients with milder severity COPD. Finally, we will conduct a small pilot imaging study to obtain preliminary characterization of [11C]PBR28 binding and [18F]FDG uptake in cohorts of individuals with COPD and healthy volunteers as a prelude to a formal clinical trial testing the efficacy of [11C]PBR28 and [18F]FDG in discriminating between macrophage-dominant and neutrophil-dominant inflammation in patients with COPD (Aim 2).

描述（由申请人提供）：慢性阻塞性肺疾病（COPD）是一种普遍的炎症性肺部疾病，需要为其量化肺部炎症的新工具，以帮助开发有效的抗炎治疗。巨噬细胞激活对疾病进展至关重要，因此，可以追踪肺部巨噬细胞募集和激活的技术对于描述COPD患者的炎症表型并评估抗炎治疗反应而言是有价值的。正电子发射断层扫描（PET）是一种非侵入性技术，可以使用[18F]氟脱氧葡萄糖（[18F] FDG）来量化肺部炎症，这是一种常用的临床示踪剂。新型PET示踪剂[11C] PBR28靶向转运蛋白（TSPO），该蛋白在活化的巨噬细胞中以高水平存在。该项目将检验总体假设，即通过PET测量的[11C] PBR28结合和[18F] FDG摄取可用于区分COPD患者的巨噬细胞主导炎症与嗜中性粒细胞炎症。 We will accomplish this by first conducting studies of TSPO expression and glucose uptake in ex vivo mouse models of macrophage activation along with microPET imaging and tissue staining to determine the specificity of [11C]PBR28 and [18F]FDG for macrophages and neutrophils in mice following virus infection- induced chronic obstructive lung disease (Aim 1).然后，我们将研究TSPO的表达和葡萄糖在极化的人外周血单核细胞中的葡萄糖摄取，以与小鼠实验和COPD患者或健康供体肺切除术时捐赠时捐赠的肺组织样品和肺组织样品中的肺组织样品和肺部的健康时，患有健康的供体和较轻的患者患者患有肺部的供体。 Finally, we will conduct a small pilot imaging study to obtain preliminary characterization of [11C]PBR28 binding and [18F]FDG uptake in cohorts of individuals with COPD and healthy volunteers as a prelude to a formal clinical trial testing the efficacy of [11C]PBR28 and [18F]FDG in discriminating between macrophage-dominant and neutrophil-dominant inflammation in COPD患者（AIM 2）。