This review covers publications on siderophores applied for molecular imaging applications, mainly for radionuclide-based imaging. Siderophores are low molecular weight chelators produced by bacteria and fungi to scavenge essential iron. Research on these molecules has a continuing history over the past 50 years. Many biomedical applications have been developed, most prominently the use of the siderophore desferrioxamine (DFO) to tackle iron overload related diseases. Recent research described the upregulation of siderophore production and transport systems during infection. Replacing iron in siderophores by radionuclides, the most prominent Ga-68 for PET, opens approaches for targeted imaging of infection; the proof of principle has been reported for fungal infections using 68Ga-triacetylfusarinine C (TAFC). Additionally, fluorescent siderophores and therapeutic conjugates have been described and may be translated to optical imaging and theranostic applications. Siderophores have also been applied as bifunctional chelators, initially DFO as chelator for Ga-67 and more recently for Zr-89 where it has become the standard chelator in Immuno-PET. Improved DFO constructs and bifunctional chelators based on cyclic siderophores have recently been developed for Ga-68 and Zr-89 and show promising properties for radiopharmaceutical development in PET. A huge potential from basic biomedical research on siderophores still awaits to be utilized for clinical and translational imaging.

0000 8853 2677grid 5361 1Division of Molecular Biology Biocenter Medical University Innsbruck Innsbruck Austria

0000 8853 2677grid 5361 1Universitätsklinik für Nuklearmedizin Medizinische Universität Innsbruck Anichstr 35 6020 Innsbruck Austria

0000 8853 2677grid 5361 1Universitätsklinik für Nuklearmedizin Medizinische Universität Innsbruck Anichstr 35 6020 Innsbruck Austria ; 0000 0000 8653 1072grid 410737 6Department of Experimental Nuclear Medicine Guangzhou Medical University Guangzhou Guangdong China

0001 1245 3953grid 10979 36Faculty of Medicine and Dentistry Institute of Molecular and Translational Medicine Palacky University Olomouc Czech Republic

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Automated Production of [68Ga]Ga-Desferrioxamine B on Two Different Synthesis Platforms

Preclinical characterisation of gallium-68 labeled ferrichrome siderophore stereoisomers for PET imaging applications

68Ga-labelled desferrioxamine-B for bacterial infection imaging

Antifungal Drugs

Hybrid Imaging of Aspergillus fumigatus Pulmonary Infection with Fluorescent, 68Ga-Labelled Siderophores

Modifying the Siderophore Triacetylfusarinine C for Molecular Imaging of Fungal Infection