Penn Quantitative MRI Resource for Pancreatic Cancer

宾夕法尼亚大学胰腺癌定量 MRI 资源

基本信息

批准号：
10011560
负责人：
Peter J ODwyer
金额：
$ 60.72万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-14 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10011560
关键词：
Advisory Committees Alleles Animals Benchmarking Biological Biology Body Size Cancer Center Cancer Etiology Cancer Patient Cessation of life Clinic Clinical Clinical Data Clinical Research Clinical Trials Collaborations Combined Modality Therapy Communities Computer software Credentialing Data Data Set Databases Development Diffusion Diffusion Magnetic Resonance Imaging Echo-Planar Imaging Extracellular Matrix Financial compensation Genetically Engineered Mouse Goals Heart Rate Hospitals Human Human Genetics Image Image Enhancement Imaging Techniques Immune In Situ Individual Industrialization Intervention Investigational Drugs Investigational Therapies Liver Location Lung Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of pancreas Methodology Methods Microscopic Mission Modality Modeling Motion Mus Pancreas Pancreatic Ductal Adenocarcinoma Patients Penetration Pharmaceutical Preparations Phase II Clinical Trials Physiologic pulse Predisposition Procedures Protocols documentation Radial Radiology Specialty Reproducibility Research Resistance Resolution Resources Respiration Standardization TP53 gene Techniques Testing The Cancer Imaging Archive Therapeutic Validation Variant Water base bioinformatics resource bulk motion chemotherapy contrast enhanced design effective therapy falls heart motion imaging biomarker imaging modality imaging study improved magnetic field mouse model mutant new therapeutic target novel novel therapeutics online resource open source outcome prediction pancreatic cancer model pancreatic neoplasm pre-clinical preclinical imaging preclinical study preclinical trial programs prospective quantitative imaging respiratory response subcutaneous success temporal measurement tool tumor tumor microenvironment web portal

项目摘要

Project Summary Preclinical quantitative imaging (QI) and mouse tumor models bridge the gap between the discovery of new therapeutic targets and the ultimate proof of their efficacy in cancer patients. The Penn Quantitative MRI Resource for Pancreatic Cancer aims to standardize quantitative imaging methods optimized for biologically relevant mouse models to accelerate the development of novel therapies for pancreatic ductal adenocarcinoma (PDA). PDA is featured by a dense stroma, which constitutes a unique tumor microenvironment that resists drug penetration and is immune suppressive. Successful stroma-directed interventions can be a vital part of effective PDA management. Although several stroma-directed drugs are being examined in the clinic, QI markers are not available for evaluating stroma responses in mice or patients. We have identified translational motion sensitive MRI markers which can detect changes of the tumor microenvironment, and we propose to examine their utility for stroma-directed interventions. However the preclinical imaging techniques are suboptimal for studying orthotopic tumors in locations susceptible to respiratory/cardiac motion such as the pancreas. Importantly, the motion-robust imaging must be achieved simultaneously with adequate temporal resolution required by the dynamic imaging protocol, the spatial resolution required to resolve the small size targets. Our prior success in the development and optimization of preclinical and clinical MRI methodology provides a roadmap to accomplish the mission of optimizing the preclinical motion-sensitive MRI techniques to match the advanced clinical benchmarks. Our Resource will leverage the substantial institutional resources including the Mouse Hospital of PENN Pancreatic Cancer Center, which provides the genetically engineered mouse (GEM) models of PDA credentialed for studying stroma-directed interventions. The strong collaboration with our industrial partner has led to the design of a co-clinical trial that includes a prospective phase-II clinical trial and a preclinical trial, where the utility of QI markers will be tested in both patients and mice responding to the same treatment of an investigational stromal drug. A multi-expertise team and an Advisory committee will join force to achieve the technical transformation, conduct the co-clinical trial and build the Resource web-portal to disseminate all workflow documents, research tools and QA/QC phantoms and to share the novel data content.

项目概要临床前定量成像 (QI) 和小鼠肿瘤模型弥补了两者之间的差距新治疗靶点的发现及其对癌症疗效的最终证明患者。宾夕法尼亚大学胰腺癌定量 MRI 资源旨在标准化针对生物学相关小鼠优化的定量成像方法加速胰腺导管新疗法开发的模型腺癌（PDA）。 PDA 具有致密的基质，构成了独特的肿瘤微环境抵抗药物渗透并具有免疫抑制作用。成功的基质定向干预可能是有效 PDA 的重要组成部分管理。尽管临床上正在检查几种基质导向药物， QI 标记物不可用于评估小鼠或患者的基质反应。我们已经确定了平移运动敏感的 MRI 标记，可以检测肿瘤微环境，我们建议检查它们对于基质定向的效用干预措施。然而，临床前成像技术对于研究来说并不是最理想的。易受呼吸/心脏运动影响的位置的原位肿瘤，例如胰腺。重要的是，运动鲁棒成像必须同时实现动态成像协议所需的足够的时间分辨率、空间分辨率解决小尺寸目标所需的分辨率。我们之前的成功临床前和临床 MRI 方法的开发和优化提供了完成优化临床前运动敏感 MRI 使命的路线图技术以匹配先进的临床基准。我们的资源将利用丰富的机构资源，包括 PENN 胰腺小鼠医院癌症中心，提供基因工程小鼠 (GEM) 模型 PDA 获得了研究基质定向干预措施的资格。强强联手与我们的工业合作伙伴一起设计了一项联合临床试验，其中包括前瞻性 II 期临床试验和临床前试验，其中 QI 标记物的效用将在对相同治疗有反应的患者和小鼠中进行测试研究基质药物。多专业团队和咨询委员会将加入力争实现技术改造、临床联合试验、打造用于传播所有工作流程文件、研究工具和 QA/QC 的资源门户网站幻影并分享新颖的数据内容。