The diagnosis of bacterial infections at deep body sites benefits from noninvasive imaging of molecular probes that can be traced by positron emission tomography (PET). We specifically labeled bacteria by targeting their iron transport system with artificial siderophores. The cyclen-based probes contain different binding sites for iron and the PET nuclide gallium-68.A panel of 11 siderophores with different iron coordination numbers and geometries was synthesized in up to eight steps, and candidates with the best siderophore potential were selected by a growth recovery assay. The probes [ 68 Ga]7 and [ 68 Ga]15 were found to be suited for PET imaging based on their radiochemical yield, radiochemical purity, and complex stability in vitro and in vivo. Both showed significant uptake in mice infected with E.coli and were able to discern infection from LPS-triggered, sterile-inflammation. The study qualifies cyclen-based artificial siderophores as readily accessible scaffolds for the in vivo imaging of bacteria. 7 and 8 from cyclen: (i) bromoacetyl bromide, K2CO3,
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