Molecular Imaging Core

分子成像核心

基本信息

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
项目类别：
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

项目摘要

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治疗和铁治疗耐药 (ARTI) 中心的一个共享资源核心是分子成像核心 (MIC) MIC 是在分子成像实验室 (MIL) 的基础上建立的，是一个中心。德克萨斯大学 MD 安德森癌症中心癌症系统成像系内的设施该中心已获得放射肿瘤学和癌症成像计划 (ROCIP) 的支持二十多年来，MIL 一直是癌症中心补助金 (P30CA016672) 的专家中心。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内和国际合作并分发了关键质粒、细胞系和报告基因虚拟 MIC 将支持 ARTI 中心的中心主题：这是为了确定铁死亡是否在获得性放射治疗（RT）抵抗中发挥重要作用。 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、 MIC 将针对这三个研究项目进行合作。与 ARTI 中心研究人员一起开发临床前成像协议并使用适当的方法进行分析生物和生化控制、稳健的重测分析以及适当时的成像统计支持（目标 1）在目标 2 中，MIC 将及时提供独特的基于质粒的生产者、报告动物、PET。试剂和荧光生物传感器，同时利用 MIL 和 MD Anderson 核心的专业知识来修改在适当的时候满足 ARTI 中心需要的试剂关于工作流程，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为 ARTI 中心研究人员提供成像分析（目标 3），MIC 将进行非侵入性分析。在肺癌和食道癌的临床前小动物模型中进行生物发光成像，以测试其效果铁死亡诱导剂（FINs）联合RT以及FINs联合免疫治疗克服帮助确定缺氧是否调节铁死亡和获得性 RT 抵抗。在项目 2 中，MIC 将进行生物发光成像来监测缺氧肿瘤的生长 RT 反应的耐药性以及 FINs、缺氧诱导因子 (HIF) 的潜在放射增敏作用激活转录因子 4 (ATF4) 抑制剂或敲除、高压氧治疗以及通过项目 3 识别肿瘤内的缺氧区域，MIC 将评估骨髓细胞扩张的作用。使用衍生自的临床前肿瘤模型赋予铁死亡对放化疗的抗性食管腺癌患者并使用 MIC 开发的新型 PET 示踪剂。不仅可以作为 ARTI 中心研究人员的资源，还可以作为其他获得性治疗耐药性的资源网络 (ARTNet) 以及其他国家癌症研究所资助的计划和举措。