Multiparametric Imaging and Molecular Probe Design Platform

该核心单元的中心目标是监测肿瘤的代谢和生理变化，以响应该联盟项目和肿瘤模型中基本细胞过程的抑制。在宏观层面上，这将由最先进的非侵入性体内成像方式提供，如正电子发射断层扫描（PET）、磁共振成像（MRI）、超偏振成像和光学成像（OI）。在分子水平上，我们将应用基于核磁共振的代谢组学。此外，这个核心单位将支持该联盟设计新的化合物，针对感兴趣的细胞过程。Pichler实验室提供了一个出色的成像平台，配备了三个专用的小动物PET扫描仪，两个7T MRI扫描仪，一个超偏振器和一个光学成像系统。几种PET示踪剂的合成针对葡萄糖代谢、脂肪酸代谢、增殖、缺氧、血管生成以及最近的衰老，在附设的内部放射药学中已经很好地建立了。多参数成像协议和分析工具以及高技能的科学和技术人员到位。有了这个装置，我们将能够提供强大的工具来揭示体内细胞和组织代谢、功能和形态的分子信息。此外，体内成像技术将辅以我们的600 MHz核磁共振对小肿瘤和组织样本的代谢组学，这对于研究某些项目中的肿瘤细胞代谢组学尤其宝贵。Poso实验室高度专注于虚拟筛选和命中优化，以识别针对感兴趣蛋白质的新药。该实验室配备了Gold、Autodock和Glide等对接程序，并且可以访问内部的天然化合物数据库以及商业上可用的化合物集合。用MD和WaterMap方法研究了脱溶效应。必要的计算能力由bw网格和芬兰csc科学计算中心有限公司的超级计算资源提供。该核心单位的专业知识将提供从宏观到分子尺度的全面代谢分析，为该联盟提供一个特殊的、具有国际高度竞争力的平台。该核心单元中可用的工具和方法将有力地促进科学项目的进展，并将导致对靶向治疗窗口的分子过程的更深层次的理解。最后，它将使联盟的合作伙伴能够开发针对已识别蛋白质的新分子。

The central aim of this core unit is to monitor metabolic and physiological changes of tumors in response to inhibition of the essential cellular processes within the projects and tumor models of this consortium. On a macroscopic level this will be provided by state-of-the-art non-invasive in vivo imaging modalities like positron emission tomography (PET), magnetic resonance imaging (MRI), hyperpolarized imaging and optical imaging (OI). On a molecular level, we will apply nuclear magnetic resonance (NMR) based metabolomics. Furthermore, this core unit will support the consortium with the design of novel compounds, targeting the cellular processes of interest. The Pichler lab provides an outstanding imaging platform that is equipped with three dedicated small animal PET scanners, two 7T MRI scanners, a hyperpolarizer and an optical imaging system. The synthesis of several PET tracers targeting glucose metabolism, fatty acid metabolism, proliferation, hypoxia, angiogenesis and recently also senescence is well established in the attached in-house radiopharmacy. Multiparametric imaging protocols and analysis tools and highly skilled scientific and technical personnel are in place. With this set up, we will be able to provide powerful tools to reveal molecular information about cell and tissue metabolism, function and morphology in vivo. Furthermore, in vivo imaging technologies will be complemented by metabolomics on small tumor and tissue samples with our 600 MHz NMR, which is particularly invaluable to study the tumor cell metabolome in some of the projects.The Poso lab is highly specialized on virtual screening and hit optimization to identify novel drugs targeting proteins of interest. The lab is equipped with docking programs like Gold, Autodock, and Glide and has an access to an in-house database of natural compounds as well as commercially available compound collections. Desolvation effects are studied by MD and WaterMap methods. The necessary computational capacity is provided by the BW-grid and supercomputing resources of the CSC-Center for Scientific Computing Ltd, Finland.The expertise of this core unit will provide a comprehensive metabolic analysis from a macroscopic down to a molecular scale, supporting the consortium with an exceptional and internationally highly competitive platform. The tools and methods available within this core unit will strongly facilitate the progress in the scientific projects and will lead to a deeper understanding of the molecular processes underlying the targeted therapeutic windows. Finally it will enable the partners of the consortium to develop novel molecules, targeting the identified proteins.