A Quantitative PET/CT Research Resource for Co-Clinical Imaging of Lung Cancer Therapies

项目摘要 这项建议的具体目标是开发和优化临床前PET定量成像的方法 用于非小细胞肺癌(NSCLC)的免疫检查点抑制(ICI)治疗。我们将利用 使用我们的肺腺癌基因工程小鼠模型(GEMM)进行的现有联合临床试验 开发、测试和实施这些方法，并建立一个网上可访问的研究资源。这个网络- 可获得的研究资源将反过来利用定量癌症成像的最新发展 使用行业标准DICOM格式的信息学。响应PAR-18-841有四个组件 对于我们的建议：(1)适当的模型，(2)包括治疗目标的联合临床试验，(3)定量 临床前和临床PET成像，以及(4)创新的癌症定量成像信息学平台。 我们的长期目标是改善非小细胞肺癌患者的预后，因为肺癌仍然是肺癌的主要原因 全球癌症死亡人数。尽管ICI治疗对一些非小细胞肺癌具有巨大的临床益处 患者中，只有约20%的NSCLC患者对抗PD1/PDL1治疗有反应。使用PET联合临床成像技术 改善非小细胞肺癌的ICI治疗面临着缺乏合适的信息学方法来捕获和跟踪的挑战 必要的元信息，临床前成像的适当反应标准，这反过来又是一种 缺乏定量的临床前PET成像方法的部分后果 临床PET成像方法。我们将以三个具体目标应对这些挑战： 1、发展和优化临床前定量成像方法和方案。这些方法 将涉及新的长寿命幻影，可以交叉校准多台临床前和临床PET扫描仪。 这将在联合临床影像研究资源计划的合作伙伴成员中进行测试。 2.在GEMM肺ICI治疗NSCLC的联合临床试验中实施优化的方法 腺癌模型和GEMM模型肺鳞状细胞癌。由此，我们将评估如何 从临床前和临床研究中收集的信息可以用来为未来的临床前研究提供信息 关于优化的鼠标成像协议和响应标准的条款。 3.使用网络可访问的开放平台，使用定量PET成像共享有关联合临床试验的数据和资源 扩展临床前小动物的DICOM标准的科学方法(开源+开放数据) 使用符合DICOM的结构进行成像，以提供必要的量化元数据。 在该项目期间开发的这些方法和资源将被分发以加速开发 通过使用联合临床提高早期肿瘤学试验的效用，从而获得所需的有效癌症治疗 用正电子发射计算机断层扫描进行研究。此外，我们将确定并可能改进PET成像的用途，如 一种早期评估联合临床免疫治疗研究反应的生物标志物 老鼠模型。

Project Abstract The specific goal of this proposal is to develop and optimize methods for quantitative pre-clinical PET imaging for immune checkpoint inhibitor (ICI) therapies in non-small cell lung cancer (NSCLC). We will leverage an existing co-clinical trial using our genetically-engineered mouse model (GEMM) of lung adenocarcinoma to develop, test and implement the methods and populate a web-accessible research resource. This web- accessible research resource will in turn leverage recent developments in quantitative cancer imaging informatics using the industry-standard DICOM format. In response to PAR-18-841 there are four components to our proposal: (1) appropriate models, (2) a co-clinical trial including a therapeutic goal, (3) quantitative preclinical and clinical PET imaging, and (4) an innovative quantitative cancer imaging informatics platform. Our longer term goal is to improve outcomes for NSCLC patients, as lung cancer is still the leading cause of cancer deaths worldwide. Although ICI therapy has been a tremendous clinical benefit for some NSCLC patients, only ~20% of NSCLC patients respond to anti-PD1/PDL1 therapy. Using PET co-clinical imaging to improve ICI therapies for NSCLC is challenged by a lack of suitable informatics methods to capture and track necessary meta-information, appropriate response criteria for preclinical imaging, which in turn is a consequence in part of the lack of quantitative preclinical PET imaging methods that are linked to quantitative clinical PET imaging methods. We will address these challenges with three Specific Aims: 1, Develop and optimize quantitative preclinical quantitative imaging methods and protocols. These methods will involve novel long-lived phantoms that can cross-calibrate multiple preclinical and clinical PET scanners. This will be tested with partner members of the Co-Clinical Imaging Research Resources Program. 2. Implement the optimized methods in our co-clinical trial of ICI treatment of NSCLC with a GEMM lung adenocarcinoma model and a GEMM model lung squamous cell carcinoma. From this we will evaluate how the information gleaned from the pre-clinical and clinical studies can be used to inform future pre-clinical studies in terms of optimized mouse imaging protocols and response criteria. 3. Share data and resources on co-clinical trials using quantitative PET imaging using a web-accessible open science approach (open source + open data) by extending the DICOM standard for pre-clinical small animal imaging with DICOM-compliant structures that provide necessary quantitative meta-data. These methods and resources developed during this project will be distributed to accelerate the development of needed effective cancer therapies by improving the utility of early-phase oncology trials using co-clinical studies with PET imaging. In addition, we will determine, and potentially improve, the utility of PET imaging as a biomarker for early assessment of response in co-clinical immunotherapy studies by using an appropriate mouse model.