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.

分子成像核心摘要 获得性抗铁治疗（阿尔蒂）中心的一个共享资源核心是 分子成像核心（MIC）。MIC是一个建立在分子成像实验室（MIL），一个中央 德克萨斯大学医学博士安德森癌症中心癌症系统成像部的一个设施 该中心获得了放射肿瘤学和癌症成像计划（ROCIP）的支持， 癌症中心补助金（P30CA016672）。二十多年来，MIL一直是 临床前成像，包括正电子发射断层扫描（PET）和生物发光成像， 已经建立了国家和国际合作，并分发了关键质粒、细胞系和报告基因， 动物对全球科学界的影响虚拟MIC将支持阿尔蒂中心的中心主题， 这是为了确定铁凋亡是否在获得性放射治疗抵抗（RT）中起主要作用。的 MIC将实施和管理精确的临床前成像支持基础设施（人员、试剂， 动物、软件和定制的硬件资源）。MIC将与 与阿尔蒂中心的研究者一起制定临床前成像方案和分析， 生物和生化控制，稳健的重测分析，以及成像统计支持（如适用） (Aim 1）。在目标2中，MIC将提供及时获取独特的基于质粒的报告基因、报告动物、PET的机会 试剂和荧光生物传感器，同时利用MIL和MD安德森核心的专业知识， 试剂，以满足阿尔蒂中心的需求。关于工作流程，MIC将提供及时的服务， 培训、访问定制的宏观和微观成像系统、高级图像分析和定制 向阿尔蒂中心研究者提供影像学分析（Aim 3）。对于项目1，MIC将执行无创性 在肺癌和食管癌的临床前小动物模型中进行生物发光成像，以测试 铁凋亡诱导剂（FINS）联合RT以及FINS联合免疫治疗， 获得性肿瘤RT抗性。以帮助确定缺氧是否调节铁凋亡和获得性RT 在项目2中，MIC将进行生物发光成像，以监测缺氧肿瘤的生长 RT反应的抵抗和FINs、缺氧诱导因子（HIF）的潜在放射增敏作用 和激活转录因子4（ATF4）抑制剂或敲低，和高压氧治疗，以及 来识别肿瘤内的缺氧区域。在项目3中，MIC将评估骨髓细胞扩增的作用， 在使用源自以下的临床前肿瘤模型赋予铁凋亡对放化疗的抵抗性中， 食管腺癌患者和使用一种新的PET示踪剂开发的MIC。MIC还将 不仅为阿尔蒂中心的研究人员提供资源，也为其他获得性耐药治疗提供资源。 网络（ARTNet）以及其他国家癌症研究所资助的计划和倡议。