Tracking M2-Like Macrophages in Cardiopulmonary Diseases by Magnetic Resonance Imaging

通过磁共振成像追踪心肺疾病中的 M2 样巨噬细胞

• 批准号: 10534128
• 负责人: Cuihua Wang
• 金额: $ 15.26万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10534128
• 关键词: Advisory Committees; Affinity; Aftercare; Anti-Inflammatory Agents; Bacteria; Binding; Biodistribution; Biological; Biological Assay; CD80 gene; Cardiopulmonary; Cells; Colony-Stimulating Factors; Communities; Data; Detection; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Drug Kinetics; Educational workshop; Equilibrium; Evolution; Fibrosis; Fucose; Functional disorder; Future; General Hospitals; Glioma; Goals; Grant; Heterogeneity; Human; Image; Immunology; In Vitro; Inflammation; Inflammatory; Interferon Type II; Interleukin-10; Interleukin-4; Knowledge; Ligands; Macrophage; Magnetic Resonance Imaging; Malignant Neoplasms; Mannose; Maps; Massachusetts; Mentorship; Monitor; Myocardial Infarction; Natural Immunity; Neoplasm Metastasis; Pathologic; Pathologic Processes; Phenotype; Play; Production; Pulmonary Heart Disease; Radiology Specialty; Reporting; Research; Research Personnel; Role; Sensitivity and Specificity; Skin wound healing; Structure-Activity Relationship; Surface; Systems Biology; TNF gene; Technology; Tissues; Training; Translating; Translations; Treatment Efficacy; Tumor Promotion; Tumor-associated macrophages; Wound models; Writing; analog; arginase; bactericide; biomedical imaging; cardiovascular imaging; career; cytotoxicity; design; experience; experimental study; fungus; healing; imaging agent; imaging biomarker; imaging modality; imaging probe; in vitro Assay; in vivo; in vivo imaging; inhibitor; instructor; lung Carcinoma; mannose receptor; medical schools; meetings; mouse model; non-invasive imaging; pathogenic virus; personalized medicine; preclinical study; prototype; repaired; response; screening; spatiotemporal; symposium; targeted agent; therapeutic target; tissue repair; tool; treatment response; tumor; tumor growth; wound healing

Project Summary I am currently an Instructor in the Department of Radiology at Massachusetts General Hospital and Harvard Medical School. My long-term career goal is to become an independent investigator in biomarker imaging development and translation to better understand and diagnose inflammation in cardiopulmonary diseases. I will perform the proposed study at the Center for Systems Biology at the Simches Research Center (CSB) and MGH’s Navy Yard campus under the mentorship of Drs. John Chen, Umar Mahmood and Mikael Pittet, who have complementary expertise in imaging agent development, cardiovascular imaging development and innate immunology. Drs. Filip Swirski and Guangbin Dong will join on the advisory committee to provide advice and guidance. In addition to the mentorship and advisory meetings, I plan to deepen and broaden my knowledge and training in biomedical imaging, immunology and cardiopulmonary pathophysiology through attending formal courses, workshops and seminars at Harvard Medical School and the Harvard community as well as attending relevant conferences in the fields. This K25 grant will provide me with the training and experience necessary to grow into an independent investigator in biomedical imaging research. Research Summary Two major activated macrophage phenotypes, classically activated macrophages (M1), which are pro- inflammatory and bactericidal, and alternatively activated macrophages (M2) which, are anti-inflammatory and reparative, play critical roles in various diseases including wound healing, myocardial infarction and cancer. The importance of macrophage phenotypes and function make them an attractive diagnostic and therapeutic target. However, in vivo detection of these cells remains challenging due to the heterogeneity and complexity of the macrophage phenotypes. Efficacious and specific in vivo tools are greatly needed. Few imaging methods have been developed to tackle this issue. Mannose receptors are a well-established marker for M2- like macrophages, which recognize and bind to terminal mannose, fucose or N-acetylglucosamine on the surface of pathogenic viruses, bacteria or fungi. We hypothesize that by screening and optimizing mannose- based ligands targeting the mannose receptor we will identify a highly efficacious magnetic resonance imaging (MRI) probe that can differentiate M2-like macrophages from M1-like macrophages. Therefore, the goals of this proposal are 1) to develop an MRI probe targeting mannose receptors to detect M2-like macrophages and validate it in a mouse model of wound healing, and 2) to apply the optimal probe to longitudinally track M2-like macrophages in mouse models of myocardial infarction and lung carcinoma, with the ultimate goal of translating this technology for human use in a future study. !

项目摘要 我目前是马萨诸塞州综合医院放射学系的讲师 医学院。我的长期职业目标是成为生物标志物成像的独立研究者 开发和翻译以更好地理解和诊断心肺疾病中的感染。我 将在Simches研究中心（CSB）和 MGH的海军院子校园在博士的心态下。 John Chen，Umar Mahmood和Mikael Pittet，谁 在成像剂开发，心血管成像开发和先天性方面拥有完整的专业知识 免疫学。博士。 Filip Swirski和Guangbin Dong将加入咨询委员会，提供建议和 指导。除了进行训练和咨询会议之外，我还计划加深和扩大我的知识 以及通过参加生物医学成像，免疫学和心肺病理生理学的培训 哈佛医学院和哈佛社区的正式课程，研讨会和下水道以及 参加该领域的相关会议。这项K25赠款将为我提供培训和经验 成长为生物医学成像研究中的独立研究者所必需的。 研究摘要 两种主要激活的巨噬细胞表型，经典活化的巨噬细胞（M1），它们是促进的 炎症性和细菌性，以及抗炎和抗炎的巨噬细胞（M2） 修复性，在各种疾病中起关键作用，包括伤口愈合，心肌梗塞和癌症。 巨噬细胞表型和功能的重要性使它们成为有吸引力的诊断和治疗 目标。但是，由于异质性和复杂性，对这些细胞的体内检测仍然挑战 巨噬细胞表型。非常需要有效的特定体内工具。很少的成像 已经开发了解决此问题的方法。 Mannose接收器是M2-的公认标记 像巨噬细胞一样，在识别并结合了末端甘露糖，富谷糖或N-乙酰葡萄糖上的巨噬细胞 致病病毒，细菌或真菌的表面。我们通过筛选和优化mannose-假设这一点 针对甘露糖受体的基于基于的配体我们将确定高效的磁共振成像 （MRI）可以将M2样巨噬细胞与M1样巨噬细胞区分开的探针。因此，目标的目标 建议是1）开发靶向甘露糖受体的MRI探针以检测M2样巨噬细胞和 在伤口愈合的小鼠模型中对其进行验证，2）将最佳探针应用于纵向跟踪M2样 心肌梗塞和肺癌的小鼠模型中的巨噬细胞，最终目标是 在未来的研究中将这项技术转换为人类使用。 呢