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: 10240470
• 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/10240470
• 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; Collaborations; Combined Modality Therapy; Communities; Computer software; Credentialing; Data; Data Set; 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; KPC model; 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; co-clinical trial; 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 ductal adenocarcinoma model; pancreatic neoplasm; pre-clinical; preclinical imaging; preclinical study; preclinical trial; programs; prospective; quantitative imaging; respiratory; response; searchable database; 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）和小鼠肿瘤模型弥合了差距 发现新的治疗靶标和其在癌症中有效性的最终证明 患者。 Penn胰腺癌的定量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 加速胰管导管的新疗法的模型 腺癌（PDA）。 PDA由密集的基质构成，构成独特 抵抗药物渗透并且免疫抑制的肿瘤微环境。 成功的基质导向干预措施可能是有效PDA的重要组成部分 管理。尽管正在诊所检查了几种基质指导的药物，但 气标记不可评估小鼠或患者的基质反应。我们 已经确定了翻译运动敏感的MRI标记，可以检测 肿瘤微环境，我们建议检查其针对基质导向的效用 干预措施。但是，临床前成像技术是次优的研究 在易受呼吸/心脏运动的位置的原位肿瘤，例如 胰腺。重要的是，必须同时实现运动型成像 动态成像协议所需的足够时间分辨率，空间 解决小尺寸目标所需的分辨率。我们先前在 临床前和临床MRI方法的开发和优化提供了 路线图要完成优化临床前运动敏感MRI的任务 与高级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，包括宾夕法尼亚州鼠标医院 癌症中心，提供基因工程的鼠标（GEM）模型 PDA认证用于研究基质指导的干预措施。强大的合作 与我们的工业合作伙伴一起，设计了一项共同临床试验，其中包括 前期II期临床试验和临床前试验，其中Qi标记的效用 将在患者和小鼠中对同一治疗的患者进行测试 研究性基质药。一个多专长的团队和咨询委员会将加入 实现技术转型的力量，进行共同临床试验并建立 资源网络门户以传播所有工作流文档，研究工具和QA/QC 幻影并共享新颖的数据内容。