Siderophores for molecular imaging applications

Abstract

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 68 Ga-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.

Modifying the Siderophore Triacetylfusarinine C for Molecular Imaging of Fungal Infection

“…PET has been widely used for molecular imaging due to the high-intensity images, limitless depth of penetration, and providing quantitative data. Among positron emitter isotopes, gallium-68 (Ga-68) is the most attractive nuclide for radiolabeling of siderophores [15]. Ga 3+ has an equal charge and a comparable radius to ferric ion (Fe 3+ ) allowing displacement of iron by Ga-68.…”

[11C]Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism

“…Recent studies have shown bacterial uptake of radiolabelled sugars and sugar alcohols that are not efficiently metabolized by humans, such as 2-deoxy-2-[ 18 F]fluorosorbitol ( 18 F-FDS), 6-[ 18 F]fluoromaltose, and 6″-[ 18 F]fluoromaltotriose 10–12 . Other innovative approaches target bacterial iron metabolism via 67 Ga or 68 Ga-siderophore complexes 13–15 . Recently we also showed that a D-amino acid derived tracer D-[methyl- 11 C]methionine ([ 11 C]D-Met) could distinguish active infection from sterile inflammation in a murine myositis model, presumably via incorporation into bacterial peptidoglycan 16 .…”

Arabinofuranose‐derived positron‐emission tomography radiotracers for detection of pathogenic microorganisms

“…In light of these concerns, several groups including ours hope to develop faster, more accurate, and higher resolution positron emission tomography (PET) tools for imaging bacterial infection. Newer radiotracers derived from maltose, para‐aminobenzoic acid (PABA), d ‐amino acids, bacterial siderophores, sorbitol, and other small‐molecules have targeted bacteria‐specific metabolism, with the potential for widespread clinical dissemination 6–12 . The sorbitol‐derived radiotracer 2‐deoxy‐2‐[ 18 F]fluoro‐sorbitol ([ 18 F]FDS), a reduced product of [ 18 F]FDG, has been studied extensively in elegant preclinical models and more recently in patients 13–15 .…”