PET imaging of radiation induced lung injury

放射性肺损伤的 PET 成像

基本信息

批准号：
10652691
负责人：
Valerie Humblet
金额：
$ 119.14万
依托单位：
COLLAGEN MEDICAL, LLC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-04 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10652691
关键词：
Acute Address Affinity Area Biopsy Cancer Patient Cessation of life Chest Chronic Clinical Collagen Collagen Type I Cyclic GMP DNA Damage Diagnosis Disease Disease Progression Dose Early Diagnosis Early treatment Etiology Exclusion Exposure to Fibrosis Formulation Free Radicals General Hospitals High Resolution Computed Tomography Hospitalization Image Infection Inflammation Inflammatory Response Injury Investigational New Drug Application Ionizing radiation Label Lung Malignant Neoplasms Malignant neoplasm of lung Massachusetts Medical Morbidity - disease rate Non-Small-Cell Lung Carcinoma Patient imaging Patients Phase Positron-Emission Tomography Production Pulmonary Edema Pulmonary Fibrosis Pulmonary Inflammation Pulmonary function tests Radiation Radiation Injuries Radiation therapy Radio Recording of previous events Recurrence Scanning Schedule Severities Signal Transduction Source Specificity Sterility Structure of parenchyma of lung Symptoms Testing Time Tissues base cGMP production cancer radiation therapy experience follow-up idiopathic pulmonary fibrosis imaging approach imaging study manufacturing process molecular imaging mortality radiation-induced lung injury side effect standard of care surveillance imaging targeted imaging tissue injury tool uptake

项目摘要

Project Summary With 2.1 million new cases in 2018, and 1.8 million deaths, lung cancer is the most common cancer in the world. Radiation therapy is the standard of care for inoperable non-small cell lung cancer and confers a significant survival benefit. Unfortunately, an important side effect of radiation therapy for cancer is Radiation Induced Lung Injury (RILI) - the direct tissue injury due to DNA damage and free radical injury, as well as the subsequent inflammatory response caused by exposure of the lungs to ionizing radiation. 50-76% of patients undergoing radiation therapy for lung cancer each year develop some form of radiation injury as seen on surveillance imaging. Not only is RILI a significant source of morbidity and mortality, but the lung’s sensitivity to radiation limits the amount of radiation which can be given to treat cancer. RILI can be divided into two phases: 1) Acute pneumonitis (1-6 months post-radiation) causing lung inflammation and edema which may require hospitalization and rarely is fatal. 2) Chronic fibrosis phase (months to years post radiation) during which smoldering inflammation causes fibrotic tissue to replace normal lung tissue and results in significant morbidity. Currently, RILI diagnosis is based on clinical history, symptoms, lung function tests, and chest imaging. RILI is typically a diagnosis of exclusion after recurrent malignancy and infection have been ruled out and rarely may require an invasive lung tissue biopsy to exclude alternative etiologies. At best, we can use the current tools to diagnose the presence of RILI, but we are unable to: 1) accurately quantify the severity and distribution of RILI 2) repeatedly assess disease activity and progression. This proposal aims to addresses these unmet needs through non-invasive molecular imaging of type 1 collagen, which is prevalent in active fibrotic disease such as RILI. We hypothesize that a newly developed positron emission tomography probe, 68Ga-CBP8, targeted to type I collagen, will enable earlier detection and accurate quantification of RILI. We further hypothesize that the use of this new targeted imaging approach will allow to better predict disease progression and thus ultimately help to identify which patients may benefit from early treatment. The affinity and specificity of 68Ga-CPB8 for type 1 collagen are well established and we have clinical experience with this agent in the imaging of idiopathic pulmonary fibrosis. Here, for the first time, we propose to use the agent to image radiation-induced lung injury. The proposal is divided into two phases. First, we aim to establish that 68Ga-CPB8 specifically accumulates in regions of RILI and can be imaged with PET. Subjects that underwent radiation therapy for lung cancer and are known to have RILI will be imaged in this proof-of-concept aim and results will be compared to high-resolution computed tomography (HRTC) images. We will conduct this study under a current IND held at Massachusetts General Hospital. In Phase 2, Collagen Medical will obtain its own IND to conduct a larger study where patients will be scanned prior to radiation therapy than followed up early when conventional HRTC imaging is not accurate. We also aim to demonstrate that PET imaging can predict disease progression after exposure to radiation in the chest area.

项目概要 2018 年肺癌新增病例达 210 万，死亡人数达 180 万，是世界上最常见的癌症。放射治疗是无法手术的非小细胞肺癌的标准治疗方法，具有显着的疗效不幸的是，癌症放射治疗的一个重要副作用是辐射引起的肺损伤。损伤（RILI）——DNA损伤和自由基损伤导致的直接组织损伤，以及随后的损伤 50-76% 接受电离辐射的患者会出现因肺部暴露而引起的炎症反应。监测显示，每年肺癌的放射治疗都会产生某种形式的放射损伤 RILI 不仅是发病率和死亡率的重要来源，而且肺部对辐射的敏感性也很高。限制了可用于治疗癌症的辐射量，RILI 可分为两个阶段： 1) 急性期。肺炎（放射后 1-6 个月）导致肺部炎症和水肿，可能需要住院治疗 2) 慢性纤维化阶段（辐射后数月至数年），在此期间闷烧。炎症导致纤维化组织取代正常肺组织并导致显着的发病率。 RILI 诊断基于临床病史、症状、肺功能测试和胸部影像学检查。排除复发性恶性肿瘤和感染后的排除诊断，很少需要进行侵入性肺组织活检以排除其他病因充其量，我们可以使用现有的工具来诊断。 RILI 的存在，但我们无法：1) 准确量化 RILI 的严重程度和分布 2) 该提案旨在通过反复评估疾病活动和进展来解决这些未满足的需求。 1 型胶原蛋白的非侵入性分子成像，这种胶原蛋白在活动性纤维化疾病（如 RILI）中很常见。我们寻求一种新开发的正电子发射断层扫描探针 68Ga-CBP8，针对 I 型胶原蛋白，将使 RILI 能够更早检测和准确量化。这种新的靶向成像方法将能够更好地预测疾病进展，从而最终有助于确定哪些患者可以从早期治疗中受益 68Ga-CPB8 对 1 型的亲和力和特异性。胶原蛋白已经很成熟，我们在特发性成像方面拥有该药物的临床经验肺纤维化，我们首次建议使用该试剂对辐射引起的肺损伤进行成像。该提案分为两个阶段，首先，我们的目标是确定 68Ga-CPB8 的具体积累。 RILI 区域，可以使用 PET 进行成像，接受过肺癌放射治疗的受试者。已知具有 RILI 的物体将在此概念验证目标中成像，并将结果与高分辨率进行比较我们将根据目前在马萨诸塞州举行的 IND 进行这项研究。在第二阶段，Collagen Medical 将获得自己的 IND，以对患者进行更大规模的研究。将在放疗前进行扫描，而不是在传统 HRTC 成像未进行时尽早进行随访我们还旨在证明 PET 成像可以预测暴露后的疾病进展。胸部区域的辐射。