Penn Quantitative MRI Resource for Pancreatic Cancer

项目摘要 临床前定量成像(QI)和小鼠肿瘤模型弥合了 新的治疗靶点的发现及其对癌症疗效的最终证明 病人。宾夕法尼亚大学胰腺癌定量磁共振资源旨在 标准化针对生物相关小鼠优化的定量成像方法 加快胰管新疗法开发的模式 腺癌(PDA)。PDA的特点是基质致密，这构成了一个独特的 抵抗药物渗透和免疫抑制的肿瘤微环境。 成功的间质导向干预可能是有效的PDA的重要组成部分 管理层。尽管几种基质导向的药物正在临床上进行检查， QI标记不能用于评估小鼠或患者的间质反应。我们 已经识别出平移运动敏感的MRI标志物，可以检测到 肿瘤微环境，我们建议检查它们对间质导向的作用 干预措施。然而，临床前成像技术对于研究来说并不理想。 易受呼吸/心脏运动影响的原位肿瘤 胰腺。重要的是，运动稳健成像必须与 动态成像协议所需的足够的时间分辨率、空间分辨率 解析小尺寸目标所需的分辨率。我们在过去的成功 临床前和临床MRI方法学的发展和优化提供了 完成优化临床前运动敏感磁共振成像任务的路线图 与先进临床基准相匹配的技术。我们的资源将利用 包括宾夕法尼亚大学胰腺医院在内的大量机构资源 癌症中心，该中心提供基因工程小鼠(GEM)模型 PDA因研究间质导向干预而获得证书。强大的协作 与我们的工业合作伙伴一起设计了一项联合临床试验，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身上进行测试 研究中的基质药物。一个多专业团队和一个咨询委员会将加入 力量实现技术改造，开展联合临床试验，建设 资源门户-用于传播所有工作流程文档、研究工具和质量保证/质量控制 幻影和共享新颖的数据内容。

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.