POSITRON EMISSION TOMOGRAPHIC IMAGING OF LUNG TRANSPLANT

肺移植的正电子发射断层成像

• 批准号: 8614184
• 负责人: Delphine L Chen
• 金额: $ 70.93万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8614184
• 关键词: Accounting; Acute; Antigen-Presenting Cells; Biological Markers; Biopsy; Bronchiolitis Obliterans; Bronchoalveolar Lavage; Cell Lineage; Cell Proliferation; Cell division; Cells; Clinical Management; Data; Development; Failure; Flow Cytometry; Fluorescence-Activated Cell Sorting; Goals; Gold; Graft Rejection; Histologic; Human; Image; Imaging Techniques; Immune; Immune Cell Activation; Immunosuppression; Immunosuppressive Agents; Infection; Inflammation; Intercept; Label; Lead; Left lung; Leukocytes; Lung; Lung Transplantation; Lung diseases; Lymph; Malignant Neoplasms; Measures; Membrane; Methods; Monitor; Mus; Organ; Outcome; Patients; Pattern; Phase; Positron; Positron-Emission Tomography; Procedures; Process; Progesterone Receptors; Proliferating; Proliferation Marker; Research Personnel; Risk; Risk Factors; Severities; Solid; Staging; Staining method; Stains; Structure of parenchyma of lung; Syndrome; T-Cell Activation; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Time; Tracer; Transplant Recipients; Transplantation; Treatment Efficacy; Treatment Protocols; analog; cell type; clinical practice; clinically relevant; fluorodeoxyglucose; glucose uptake; healthy volunteer; improved; in vitro Model; lung imaging; monocyte; mouse model; neutrophil; novel; peripheral blood; response; sigma-2 receptor; uptake

Lung transplantation is the treatment of choice for end-stage lung disease, but survival after lung transplant remains disappointingly low. Acute rejection episodes put lung grafts at greater risk of failing. However, acute rejection is often clinically silent and difficult to detect by any means other than biopsy, which requires an invasive procedure. Therefore, noninvasive methods for detecting and quantifying the presence of acute rejection could potentially improve outcomes for lung transplant recipients by improving our ability to detect acute rejection that requires treatment. Because T cells must proliferate in the lungs to cause acute rejection, we propose using the novel positron emission tomography (PET) tracer [18F]ISO-1, which targets the proliferation marker sigma-2 receptor, also recently characterized as the progesterone receptor membrane component-1 (PGRMC1), to image T cell activation in lung grafts. We have shown that PET imaging with [18F]fluorodeoxyglucose ([18F]FDG) also detects acute rejection and can measure its response to treatment; therefore, we will evaluate the ability of [18F]ISO-1 and [18F]FDG to detect acute rejection in a novel mouse model of left lung transplantation and in human lung transplant recipients.

肺移植是终末期肺病的首选治疗方法，但肺移植后的生存率仍然很低，令人失望。急性排斥反应使肺移植面临更大的风险 失败。然而，急性排斥反应通常在临床上是无症状的，并且很难通过活检以外的任何方式检测到，而活检需要侵入性手术。因此，用于检测和量化急性排斥反应存在的非侵入性方法可能会通过提高我们检测需要治疗的急性排斥反应的能力来改善肺移植受者的预后。由于 T 细胞必须在肺部增殖才能引起急性排斥反应，因此我们建议使用新型正电子发射断层扫描 (PET) 示踪剂 [18F]ISO-1，其目标是增殖标记 sigma-2 受体，最近也被定性为孕激素受体膜成分 1 (PGRMC1)，用于对肺移植物中的 T 细胞激活进行成像。我们已经证明，使用 [18F] 氟脱氧葡萄糖 ([18F]FDG) 进行 PET 成像也可以检测急性排斥反应，并可以测量其对治疗的反应；因此，我们将评估 [18F]ISO-1 和 [18F]FDG 在新型左肺移植小鼠模型和人肺移植受者中检测急性排斥反应的能力。