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

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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.