Molecular Imaging Core

分子成像核心

• 批准号: 10517142
• 负责人: David Piwnica-Worms
• 金额: $ 21.57万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10517142
• 关键词: Animal Model; Animals; Basic Science; Biochemical; Biological; Bioluminescence; Biosensor; Cancer Biology; Cancer Center; Cell Culture Techniques; Cell Line; Chemicals; Clinical; Collaborations; Communities; Computer software; Custom; Data; Esophageal Adenocarcinoma; Funding; Genetic Engineering; Genomics; Goals; Grant; Human; Human Resources; Hyperbaric Oxygenation; Hypoxia; Hypoxia Inducible Factor; Image; Immunotherapy; Individual; Infrastructure; Institution; International; Iron; Laboratories; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of lung; Mammalian Cell; Modeling; Molecular Biology; Monitor; Myeloid Cells; National Cancer Institute; Patients; Plasmids; Play; Positron-Emission Tomography; Pre-Clinical Model; Production; Protocols documentation; Radiation; Radiation Oncology; Radiation therapy; Radiosensitization; Reagent; Reporter; Research Activity; Research Personnel; Research Project Grants; Resistance; Resource Sharing; Resources; Risk; Role; Sampling; Services; Site; Testing; Therapeutic Agents; Time; Tracer; Training; Translating; Translational Research; University of Texas M D Anderson Cancer Center; activating transcription factor 4; base; bioluminescence imaging; cancer cell; cancer imaging; chemoradiation; cohort; design; experience; experimental study; imaging program; imaging system; inhibitor; knock-down; microscopic imaging; molecular imaging; novel; novel therapeutics; pre-clinical; preclinical imaging; programs; radiation resistance; radiation response; therapy resistant; tumor; tumor growth; tumor hypoxia; virtual

Molecular Imaging Core Summary The one shared resource core of the Acquired Resistance to Therapy and Iron (ARTI) Center is the Molecular Imaging Core (MIC). The MIC is a build out of the Molecular Imaging Laboratory (MIL), a central facility within the Department of Cancer Systems Imaging at The University of Texas MD Anderson Cancer Center that has received support from The Radiation Oncology and Cancer Imaging Program (ROCIP) under the Cancer Center Grant (P30CA016672). For more than two decades, the MIL has been an expert hub for preclinical imaging, including positron emission tomography (PET) and bioluminescence imaging, and has already established national and international collaborations and distributed key plasmids, cell lines, and reporter animals to the global scientific community. The virtual MIC will support the central theme of the ARTI Center, which is to determine whether ferroptosis plays a major role in acquired resistance to radiation therapy (RT). The MIC will implement and manage the precise, preclinical imaging support infrastructure (personnel, reagents, animals, software, and customized hardware resources) for the three research projects. The MIC will collaborate with ARTI Center investigators in developing preclinical imaging protocols and analyses with appropriate biological and biochemical controls, robust test-retest analysis, and imaging statistical support when appropriate (Aim 1). In Aim 2, the MIC will provide timely access to unique plasmid-based reporters, reporter animals, PET reagents, and fluorescent biosensors, while leveraging MIL and MD Anderson cores’ expertise to modify reagents when appropriate to meet ARTI Center needs. Regarding workflow, the MIC will provide timely service, training, access to customized macro- and microscopic imaging systems, premium image analytics, and custom imaging analysis to ARTI Center investigators (Aim 3). For Project 1, the MIC will perform noninvasive bioluminescence imaging in preclinical small animal models of lung and esophageal cancer to test the effects of ferroptosis inducers (FINs) combined with RT as well as FINs combined with immunotherapy in overcoming acquired tumor RT resistance. To help determine whether hypoxia modulates ferroptosis and acquired RT resistance in Project 2, the MIC will perform bioluminescence imaging to monitor hypoxic tumor growth resistance in response to RT and the potential radiosensitizing effects of FINs, hypoxia-inducible factor (HIF) and activating transcription factor 4 (ATF4) inhibitors or knockdown, and hyperbaric oxygen therapy as well as to identify hypoxic regions within tumors. With Project 3, the MIC will assess the role of myeloid cell expansion in conferring ferroptosis resistance to chemoradiation therapy using preclinical tumor models derived from esophageal adenocarcinoma patients and using a novel PET tracer developed by the MIC. The MIC will also serve as a resource for not only ARTI Center investigators, but also for other Acquired Resistance to Therapy Network (ARTNet) as well as for other National Cancer Institute-funded programs and initiatives.

分子成像核心总结 获得的对治疗和铁（ARTI）中心的抵抗力的共享资源核心是 分子成像核心（MIC）。麦克风是从分子成像实验室（MIL）的建筑物，一个中央 德克萨斯大学MD Anderson Cancer的癌症系统成像系中的设施 在辐射肿瘤学和癌症成像计划（ROCIP）下得到支持的中心 癌症中心赠款（P30CA016672）。二十年来，MIL一直是专家枢纽 临床前成像，包括正电子发射断层扫描（PET）和生物发光成像，并具有 已经建立了国家和国际合作，并分发了关键质粒，细胞系和记者 全球科学界的动物。虚拟麦克风将支持Arti Center的中心主题， 这是为了确定铁凋亡是否在获得的放射治疗（RT）中起主要作用。 麦克风将实施和管理精确的临床前成像支持基础架构（人员，试剂， 三个研究项目的动物，软件和定制硬件资源）。麦克风将合作 与Arti中心研究人员一起开发临床前成像协议和适当的分析 适当的生物学和生化控制，可靠的测试 - 重测分析和成像统计支持 （目标1）。在AIM 2中，麦克风将及时访问独特的基于质粒的记者，记者动物，PET 试剂和荧光生物传感器，同时利用MIL和MD Anderson Core的专业知识来修改 适合满足ARTI中心需求的试剂。关于工作流程，麦克风将提供及时的服务， 培训，访问定制的宏观和微观成像系统，高级图像分析以及自定义 对ARTI中心研究人员的成像分析（AIM 3）。对于项目1，麦克风将执行无创 在肺癌和食道癌的临床前小动物模型中的生物发光成像，以测试 结合RT和FINS结合免疫疗法的脂肪吞噬作用诱导剂（FINS）在克服中 获得的肿瘤RT抗性。有助于确定缺氧是否调节铁铁作用并获得了RT 在项目2中的抗性，MIC将执行生物发光成像以监测低氧肿瘤的生长 响应RT的耐药性以及FINS的潜在放射敏化作用，缺氧诱导因子（HIF） 以及激活转录因子4（ATF4）抑制剂或敲低以及高压氧疗法以及 鉴定肿瘤中的低氧区域。使用项目3，麦克风将评估髓样细胞扩展的作用 使用源自临床前肿瘤模型，以抗化学疗法的抗性性毒性抗性 食管腺癌患者，并使用麦克风开发的新型宠物示踪剂。麦克风也将 不仅是ARTI中心调查人员的资源，还可以作为其他获得的治疗抵抗 网络（ARTNET）以及其他国家癌症研究所资助的计划和计划。