Non-invasive molecular and morphological imaging of platelets and platelet targets

该子项目旨在对活生物体中的血小板和相关目标结构进行非侵入性成像，并使用高分辨率扫描离子电导显微镜（SICM）对单细胞水平上的激活过程进行成像。该子项目的重点是创新成像，有3个优先事项：1）开发和验证用于疾病过程中血小板靶结构非侵入性成像的分子标记物，2）评价新的TK报告小鼠，用于PET血小板非侵入性成像，3）应用高分辨率荧光SICM成像单个活细胞的功能状态。对于研究小组内的不同合作伙伴，该子项目提供了一个小动物和一个临床平移成像平台[正电子发射断层扫描（PET），光学成像（OI），磁共振断层扫描（MRT），计算机断层扫描（CT），组合成像（PET/MRT）和单个活细胞亚细胞结构的高分辨率显微镜（SICM）]。这些技术与联合体内的不同合作伙伴相结合，将大大补充这些次级项目。利用我们在放射性标记和生物标志物和成像方法开发方面的专业知识，我们将可视化疾病过程中的血小板靶结构，以获得有关脆弱性，炎症和血管生成的信息。PET和MRT的组合在心血管医学中特别重要，以便将放射性标记的生物标志物的积累精确地归因于形态结构或允许确定除了分子和解剖信息之外的功能参数。此外，我们将开发一种新的转基因小鼠模型与PET相结合，以首次对健康和患病生物体中血小板的生物分布和寿命进行成像。协同非侵入性成像，荧光SICM将提供有关血小板功能的单细胞水平的信息。PET/MR成像的所有必要方法都是在我们的实验室建立的。除了[18 F]FDG，我们还将使用示踪剂对缺氧区域（[18 F]FMISO）或血管生成（[64 Cu]RGD）进行成像。特异性抗体将与螯合剂DOTA结合，随后用64 Cu进行放射性标记。长寿命的同位素还可以在体内追踪血小板或T细胞数天。血小板机制与血管生成和缺氧过程密切相关。现有的一系列方法构成了根据不同的KFO分项目的专题优先事项建立创新成像的基础。

This subprojects aims for non-invasive imaging of thrombocytes and relevant target structures in the living organism and using high-resolution scanning ion conductance microscopy (SICM) to image the process of activation on a single-cell level. The focus of this subproject is on innovative imaging with 3 priorities: 1) Development and validation of molecular markers for the non-invasive imaging of thrombocytic target structures in the process of disease, 2) evaluation of a new TK-reporter mouse for non-invasive imaging of thrombocytes with PET, and 3) application of highresolution fluorescence-SICM for the imaging of functional states in a single living cell. To the different cooperation partners within the research group this subproject offers a small animal and a clinical-translational imaging platform [positron-emission-tomography (PET), opticalimaging (OI), magnetic resonance tomography (MRT), computer tomography (CT), combined imaging (PET/MRT), and high-resolution microscopy (SICM) of sub-cellularstructures of a single living cell]. In combination with the different cooperation partners within the consortium these technologies will significantly complement the subprojects. Using our expertise in radiolabeling and in the development of biomarkers and imaging methods we will visualize thrombocytic target structures in the process of disease to gain information about vulnerability, inflammation, and angiogenesis. The combination of PET and MRT is especially important in cardiovascular medicine in order to precisely attribute the accumulation of a radiolabeled biomarker to a morphological structure or to allow the determination of functional parameters in addition to molecular and anatomical information. Further, we will develop a new transgenic mouse model in combination with PET to image,for the first time,the biodistribution and lifespan of thrombocytes in the healthy and diseased organism. Synergisticallyto non-invasive imaging, fluorescence-SICM will give information about thrombocyte function on the level of single cells. All necessary methods for PET/MR imaging are established in our laboratory. Next to [18F]FDG we will also use tracers for imaging hypoxic areas ([18F]FMISO) or angiogenesis ([64Cu]RGD). Specific antibodies will be conjugated with the chelatorDOTA and will subsequently be radiolabeled with 64Cu. Long-lived isotopes also allow in vivo-tracking of thrombocytes or T-cells for several days.Thrombocytic mechanisms are closely connected to angiogenetic and hypoxic processes. The existing spectrum of methods forms the basis for the establishment of innovative imaging, based on the thematic priorities of the different KFO-subprojects.