MR-PET for a Small Animal Imaging Center

描述(由申请人提供)：本申请，研究和研究基础设施“大机遇”(GO)拨款(RFA-OD-09-004)将集中在“比较肿瘤学研究”，并要求资金为一个独特的最先进的磁共振动物扫描仪的PET插入物，这将被许多生物医学研究实验室用作一个开放的科学资源，对翻译肿瘤学研究的重大影响。有30名首席研究人员和37个同行评议的研究项目得到了这项申请的支持，其中包括来自MSKCC以外9个机构的项目。PET和MR数据的同时采集将用于新型双MR-PET造影剂的研究、同步动力学、代谢的生化研究，以及研究标记抗体的分布以及低氧、肿瘤灌注异质性对摄取、靶向和疗效的影响。许多生理现象(如缺氧、灌流、药代动力学)会发生剧烈的变化，不同的动物之间存在差异，而造影剂/放射性示踪剂的摄取和分布可能取决于不同的时变生理参数，因此同步获取是至关重要的。我们与Cherry博士的合作设想为MSKCC建造一种PET插入物，我们将提供核磁共振(乳酸脉冲序列、定量、射频线圈)和化学专业知识。我们将评估PET插件在4.7T和7T下对MR图像和光谱质量的影响，以及这两种磁铁对PET性能的影响，并将这些数据提供给Cherry博士。我们将改进和开发用于乳酸检测和成像的新脉冲序列，这些序列将经常与同时进行的氟脱氧葡萄糖(FDG)PET扫描一起使用，因为两者都在测量糖酵解的不同方面，并且是预后的标志。一个关键的发展将是一个隔离室，以便允许来自许多机构的调查人员使用成像设备，并将来自不同机构的动物交叉污染的风险降至最低。这个小室的设计目的是将动物与扫描仪隔离，除了一个用于吸入麻醉和其他气体的端口外，还将有一个用于呼吸、体温和心脏监测的端口，以减少发病率和提高图像质量。MSKCC是开发和翻译用于癌症成像和治疗的放射性标记小分子、多肽和抗体的世界领先者。我们可以获得用于正电子发射计算机断层扫描研究的广泛的放射性核素，以及化学专业知识，用19F、Fe或Gd对它们进行双重标记，以生产可由磁共振和正电子发射计算机断层扫描显示的试剂。我们将在PET插入物交付之前开发隔离室、乳酸检测方法和新型双模式造影剂，以便在交付后立即使用。MR-PET扫描仪将支持37个不同的项目，这些项目将从这项研究中产生重大好处。如果获得资金，该项目将立即启动，并加强多学科研究和具有广泛不同背景的研究人员之间的互动，从而在癌症护理方面取得新的突破。 公共卫生相关性：相关性本申请为研究和研究基础设施“重大机遇”(GO)拨款(RFAOD-09-004)，将重点放在“比较肿瘤学研究”上，并为MR动物扫描仪的独特正电子发射断层扫描(PET)插件申请资金，该扫描仪将被许多生物医学研究实验室用作开放的科学资源，对转译癌症研究产生重大影响。

DESCRIPTION (provided by applicant): This application, for a Research and Research Infrastructure "Grand Opportunities" (GO) grant (RFA- OD-09-004) will focus on "Comparative Oncology Research" and requests funds for a unique state of the art PET insert for an MR animal scanner which will be used by numerous biomedical research laboratories as an open scientific resource, with a major impact on translational oncology research. There are 30 principal investigators and 37 peer reviewed research projects supported by this application including projects from 9 institutions outside MSKCC. Simultaneous acquisition of PET and MR data will be used for studies of novel dual MR-PET contrast agents, concurrent kinetics, biochemical studies of metabolism, and to study the distribution of labeled antibodies and the effects of hypoxia, tumor perfusion heterogeneity on uptake, targeting and efficacy. Many physiological phenomena (such as hypoxia, perfusion, pharmacokinetics) undergo acute changes, vary from animal to animal, and contrast/radiotracer agent uptake and distribution may depend on different time varying physiological parameters so simultaneous acquisition is critical. Our collaboration with Dr. Cherry envisages construction of a PET insert for MSKCC, and we will provide NMR (lactate pulse sequences, quantitation, radiofrequency coils) and chemistry expertise. We will evaluate the effect of the PET insert on MR image and spectral quality at both 4.7T and 7T and the effect of both magnets on PET performance and provide this data to Dr. Cherry. We will improve and develop novel pulse sequences for lactate detection and imaging which will be used frequently with concurrent fluorodeoxyglucose (FDG) PET scanning since both are measuring different aspects of glycolysis and are markers of prognosis. A critical development will be an isolation chamber in order to allow investigators from many institutions to use the imaging equipment and minimize the risk of cross contamination of animals from different institutions. This chamber is designed to isolate the animal from the scanner and will have ports for respiratory, temperature and cardiac monitoring to decrease morbidity and improve image quality, in addition to a port for inhalation anesthesia and other gases. MSKCC is a world leader in development and translation of radiolabeled small molecules, peptides and antibodies for the imaging and therapy of cancer. We have access to a broad gamut of radionuclides for PET studies and the chemistry expertise to dual label them with 19F, Fe or Gd to produce agents that can be visualized by both MR and PET. We will develop the isolation chamber, lactate detection methods, and novel dual modality contrast agents prior to the delivery of the PET insert for immediate use upon delivery. The MR-PET scanner will support 37 different projects that will yield significant benefit form this research. This project will be started immediately if funded and enhance multidisciplinary research and interactions between investigators of broadly different background, thereby leading to new breakthroughs in cancer care. PUBLIC HEALTH RELEVANCE: Relevance This application, for a Research and Research Infrastructure "Grand Opportunities" (GO) grant (RFAOD- 09-004) will focus on "Comparative Oncology Research" and requests funds for a unique state of the art Positron Emission Tomography (PET) insert for an MR animal scanner which will be used by numerous biomedical research laboratories as an open scientific resource, with a major impact on translational cancer research.