Penn Quantitative MRI Resource for Pancreatic Cancer

宾夕法尼亚大学胰腺癌定量 MRI 资源

• 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
• 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

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.

项目摘要 临床前定量成像（QI）和小鼠肿瘤模型差距 新的治疗靶点的发现及其对癌症疗效的最终证明 患者Penn胰腺癌定量MRI资源旨在 优化用于生物学相关小鼠的标准化定量成像方法 加速胰腺导管炎新型治疗方法开发的模型 腺癌（PDA）。PDA的特点是基质致密，这构成了一个独特的 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研究几种基质导向药物， QI标记物不可用于评价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标记物，其可以检测 肿瘤微环境，我们建议检查它们在基质定向 干预措施。然而，临床前成像技术对于研究 易受呼吸/心脏运动影响的原位肿瘤，例如 胰腺重要的是，必须同时实现运动鲁棒成像， 动态成像协议所需的足够的时间分辨率， 解决小尺寸目标所需的分辨率。我们之前在 临床前和临床MRI方法的开发和优化提供了一种 完成优化临床前运动敏感MRI的使命的路线图 与先进的临床基准相匹配的技术。我们的资源将利用 大量的机构资源，包括宾州胰腺癌小鼠医院 癌症中心，提供基因工程小鼠（GEM）模型 PDA有资格研究基质定向干预。的大力协作 与我们的工业合作伙伴一起设计了一项联合临床试验， 前瞻性II期临床试验和临床前试验，其中QI标志物的效用 将在患者和小鼠中进行测试， 研究基质药物。一个多专业团队和一个咨询委员会将加入 力实现技术改造，开展联合临床试验，打造 传播所有工作流程文件、研究工具和QA/QC的资源门户网站 虚拟现实和共享新的数据内容。