Siderophore based molecular imaging of pulmonary infections

基于铁载体的肺部感染分子成像

• 批准号: 10736423
• 负责人: Nalinikanth Kotagiri
• 金额: $ 67.89万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736423
• 关键词: Acinetobacter; Acute; Affinity; Antibiotic Therapy; Antibiotics; Bacteria; Bacterial Infections; Bacterial Model; Binding; Biodistribution; Biological Markers; Chronic Obstructive Pulmonary Disease; Clinical; Color; Communicable Diseases; Complex; Contrast Media; Copper; Detection; Development; Differential Diagnosis; Disease; Disease model; Enterobacter; Enterobacteriaceae; Exhibits; Family; Foundations; Goals; Gram-Negative Bacteria; Hospitalization; Imaging Device; Infection; Influenza A Virus, H3N2 Subtype; Innate Immune System; Iron; Klebsiella; Klebsiella pneumoniae; Label; Ligands; Lung; Lung infections; Membrane; Membrane Transport Proteins; Metals; Modeling; Monitor; Morbidity - disease rate; Multi-Drug Resistance; Mus; Myositis; Organism; Pathogenicity; Patients; Performance; Play; Pneumonia; Positron-Emission Tomography; Property; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas aeruginosa pneumonia; Radioisotopes; Reporter; Respiratory Failure; Role; Sensitivity and Specificity; Siderophores; Specimen; Sputum; Surrogate Markers; Techniques; Time; Treatment Cost; Treatment Efficacy; Viral; Virus Diseases; X-Ray Computed Tomography; clinically relevant; co-infection; imaging agent; imaging modality; imaging probe; improved; in vivo; in vivo evaluation; influenzavirus; innovation; metal chelator; molecular imaging; mortality; mouse model; new technology; nuclear imaging; pathogen; pyochelin; quantitative imaging; real-time images; receptor; respiratory; screening; technology platform; uptake; yersiniabactin

PROJECT SUMMARY Chronic obstructive pulmonary disease (COPD) is a progressive, debilitating respiratory condition with a clinical course that is punctuated by acute exacerbations (AECOPD) ranging from self-limited episodes to florid respiratory failure. AECOPD are most often precipitated by viral and/or bacterial infections. The bacterial organisms that commonly play pathogenic role in AECOPD are Pseudomonas, Klebsiella, Acinetobacter, and Enterobacter, and multidrug resistant Pseudomonas and Klebsiella pneumoniae are a common cause of secondary pneumonias in hospitalized patients with COPD. The change in color of sputum indicative of purulence that is often used as a surrogate marker for the presence of bacterial infection is a late, inconsistent, nonspecific and insensitive biomarker; it cannot distinguish between viral and bacterial infection, and many patients with AECOPD do not produce sputum at all. The availability of a targeted, pathogen-specific and sensitive imaging modality that could detect bacteria in the lower airways and differentiation bacterial from viral infection non-invasively would advance our understanding of AECOPD and facilitate development of preemptive treatment paradigms. In this proposal, we intend on using these unique bacterial membrane transporters on bacteria, and their distinct metallophores as PET reporter probes to localize and identify pathogenic live bacteria in AECOPD. We will also evaluate the specificity and sensitivity of the robes in identifying the bacteria in co- infection models with influenza virus (H3N2). We will further evaluate the responsiveness of the PET imaging probe and modality to different antibiotics, against several clinical isolates of K. pneumoniae and P. aeruginosa. If successful, the probes would be able to assist with identifying subclinical bacterial colonization of in patients with AECOPD, to determine if the bacteria that are ultimately responsible for the infection are the same strains that was found to be colonizing. This project will lay the foundation for a new technology platform that will open avenues to explore the possibility of using the diverse array of metallophores as contrast agents for imaging the entire repertoire of pathogenic infections.

项目摘要 慢性阻塞性肺疾病（COPD）是一种临床上进行的，令人衰弱的呼吸系统疾病 急性加重（AECOPD）从自限制的情节到佛罗里达 呼吸衰竭。 AECOPD通常是由病毒和/或细菌感染引起的。细菌 通常在AECOPD中起致病作用的生物是假单胞菌，克雷伯菌，acinetobacter和 肠杆菌，耐多药假单胞菌和肺炎克雷伯菌是常见的原因 住院COPD患者的次要肺炎。痰颜色的变化表示 通常用作细菌感染存在的替代标记的纯度是一个晚期，不一致的， 非特异性和不敏感的生物标志物；它无法区分病毒和细菌感染，许多 AECOPD的患者根本不会产生痰液。针对性，病原体特异性和 敏感的成像方式可以检测到下部气道中的细菌，并分化了细菌与病毒的细菌 非侵入性感染将提高我们对AECOPD的理解，并有助于发展先发制人 治疗范例。在此提案中，我们打算在上使用这些独特的细菌膜转运蛋白 细菌及其独特的金属噬菌体作为宠物报道探针，以定位和鉴定致病性活细菌 在aecopd中。我们还将评估长袍在识别共同细菌方面的特异性和敏感性 流感病毒感染模型（H3N2）。我们将进一步评估宠物成像的响应能力 对不同抗生素的探针和模态，对肺炎链球菌和铜绿假单胞菌的几种临床分离株。 如果成功，探针将能够协助鉴定患者的亚临床细菌定殖 使用AECOPD，确定最终导致感染的细菌是否是相同的菌株 发现那是殖民的。该项目将为一个新技术平台奠定基础，该平台将开放 探索使用各种金属泳道作为对比剂的可能性的途径 致病感染的整个曲目。