Fibrin-PET Imaging to Detect Aging Associated Lung Injury in Idiopathic Pulmonary Fibrosis

纤维蛋白-PET 成像检测特发性肺纤维化中与衰老相关的肺损伤

• 批准号: 10023256
• 负责人: Barry S. Shea
• 金额: $ 4.65万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2021-09-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10023256
• 关键词: Age; Aging; Alveolar; Binding; Biological; Biological Process; Blood Vessels; Breathing; Cell physiology; Cessation of life; Chronic; Cicatrix; Coagulation Process; Complex; Data; Deposition; Diagnosis; Disease; Disease Progression; Environmental Risk Factor; Equilibrium; Extravasation; Fibrin; Fibrosis; Future; Heterogeneity; Human; Imaging Techniques; Impairment; Incidence; Individual; Injury; Lead; Link; Lung; Lung diseases; Measures; Medical; Methods; Microscopic; Modeling; Mus; Outcome; Pathogenesis; Pathologic; Patients; Peptide Hydrolases; Plasma; Play; Population; Positron-Emission Tomography; Predisposition; Process; Pulmonary Fibrosis; Respiratory physiology; Role; Signal Pathway; Structure; Structure of parenchyma of lung; Techniques; Testing; Therapeutic Intervention; Thrombin; Time; Tissues; Vascular Permeabilities; Vital capacity; attenuation; human subject; idiopathic pulmonary fibrosis; individual patient; inhibitor/antagonist; injured; lung injury; molecular imaging; mouse model; novel; outcome forecast; repaired; respiratory; response; restoration; tissue injury; tool; trend; wound healing

Idiopathic pulmonary fibrosis (IPF) is a severe, chronic, aging-associated respiratory illness of unknown cause in which normal lung tissue is progressively replaced by scarring (fibrosis). This steady accumulation of scarring leads to impaired lung function, difficulty breathing, and eventually death, with an average survival of only 3-5 years after diagnosis. The current prevailing hypothesis is that IPF occurs as a result of aberrant or over-exuberant wound-healing responses to repetitive, microscopic lung injuries, due to a complex interplay of aging, host susceptibility, and environmental factors. One hallmark of lung injury is extravascular coagulation with subsequent intra-alveolar fibrin deposition. The overall hypotheses of this project are that in IPF 1) there is ongoing lung injury, 2) aging is associated with more severe lung injury, and 3) the extent of lung injury correlates with disease activity and pace of progression. To assess ongoing lung injury in IPF patients, we will use a novel molecular imaging technique, fibrin-PET, to measure lung fibrin deposition in human subjects. Specifically, we propose the following: Specific Aim 1: To determine whether ongoing lung injury can be detected in the lungs of IPF patients by fibrin-PET imaging. We hypothesize that IPF patients have ongoing lung injury, and that increased lung fibrin deposition is a manifestation of this injury. To test this hypothesis, we will perform positron emission tomography (PET) with a fibrin-specific probe, 64Cu-FBP8, to compare lung fibrin deposition in IPF patients and healthy controls. Specific Aim 2: To determine whether aging is associated with increased lung injury in IPF. We hypothesize that aging is associated with a greater extent of lung injury in IPF. To test this hypothesis, we will determine whether the extent of lung fibrin deposition, as determined by fibrin-PET imaging, correlates with increasing age in IPF. Specific Aim 3: To determine whether the extent of lung injury correlates with disease activity in IPF. We hypothesize that the extent of ongoing lung injury correlates with pace of progression, i.e. disease activity, in IPF. To test this hypothesis, we will determine whether the extent of lung fibrin deposition, as determined by fibrin-PET imaging, correlates with rate of forced vital capacity (FVC) decline in IPF.

特发性肺纤维化（IPF）是一种原因不明的严重、慢性、衰老相关的呼吸道疾病 其中正常的肺组织逐渐被瘢痕形成（纤维化）所取代。这种稳定的积累 瘢痕形成导致肺功能受损、呼吸困难，最终死亡，平均存活率为 诊断后3-5年。目前流行的假设是IPF是由于异常或 过度旺盛的伤口愈合反应重复，微观肺损伤，由于复杂的相互作用， 老化、宿主易感性和环境因素。肺损伤的一个标志是血管外凝血 随后肺泡内纤维蛋白沉积。本项目的总体假设是，在指规数1）中， 持续性肺损伤，2）年龄与更严重的肺损伤相关，3）肺损伤的程度 与疾病活动和进展速度相关。为了评估IPF患者的持续性肺损伤，我们将 使用一种新的分子成像技术，纤维蛋白PET，测量人类受试者的肺纤维蛋白沉积。 具体而言，我们提出以下建议： 具体目的1：确定是否可以在IPF患者的肺部检测到持续性肺损伤 通过纤维蛋白PET成像我们假设IPF患者存在持续性肺损伤， 纤维蛋白沉积是这种损伤的表现。为了验证这一假设，我们将进行正电子发射 使用纤维蛋白特异性探针64 Cu-FBP 8进行断层扫描（PET），以比较IPF患者的肺纤维蛋白沉积， 健康对照 具体目标2：确定年龄是否与IPF肺损伤增加相关。我们 假设年龄与IPF中更大程度的肺损伤相关。为了验证这个假设，我们将 通过纤维蛋白PET成像确定肺纤维蛋白沉积的程度是否与 IPF的年龄增长。 具体目标3：确定肺损伤程度是否与IPF的疾病活动相关。 我们假设持续性肺损伤的程度与进展速度相关，即疾病活动度， 在IPF。为了检验这一假设，我们将确定肺纤维蛋白沉积的程度，如通过 纤维蛋白PET成像与IPF患者用力肺活量（FVC）下降率相关。