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

这一子项目旨在对活体中的血小板和相关靶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)在单细胞水平上成像激活过程。这个子项目的重点是创新的成像，有三个优先事项：1)开发和验证分子标记，用于疾病过程中的血小板靶标结构的非侵入性成像；2)评估一种新的TK报告小鼠，用于PET对血小板的非侵入性成像；以及3)高分辨率荧光-SICM的应用，用于单个活细胞的功能状态成像。这个子项目为研究小组内的不同合作伙伴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)、联合成像(PET/MRT)和高分辨率显微镜(SICM)]。这些技术将与联合体内的不同合作伙伴结合起来，对次级项目起到很大补充作用。利用我们在放射性标记以及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标结构，以获得有关脆弱性、炎症和血管生成的信息。PET和MRT的结合在心血管医学中尤其重要，以便准确地将放射性标记生物标记物的积累归因于形态结构，或者允许确定除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，并与PET相结合，首次成像血栓细胞在健康和患病生物体内的生物分布和寿命。与非侵入性成像相比，荧光SICM将在单细胞水平上提供有关血小板功能的信息。在我们实验室建立了所有必要的PET/MR成像方法。除了[18F]FDG，我们还将使用示踪剂对缺氧区([18F]FMISO)或血管生成([64Cu]RGD)进行成像。特定的抗体将与螯合剂DOTA偶联，随后将用64Cu进行放射性标记。长寿命的同位素还可以在体内跟踪数天的血栓细胞或T细胞。血栓机制与血管生成和缺氧过程密切相关。根据不同KFO分项目的主题优先事项，现有的各种方法构成了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.