Invasive fungal infections have become a major challenge for public health, mainly due to the growing numbers of immunocompromised patients, with high morbidity and mortality. Currently, conventional imaging modalities such as computed tomography and magnetic resonance imaging contribute largely to the noninvasive diagnosis and treatment evaluation of those infections. These techniques, however, often fall short when a fast, noninvasive and specific diagnosis of fungal infection is necessary. Molecular imaging, especially using nuclear medicine-based techniques, aims to develop fungal-specific radiotracers that can be tested in preclinical models and eventually translated to human applications. In the last few decades, multiple radioligands have been developed and tested as potential fungal-specific tracers. These include radiolabeled peptides, antifungal drugs, siderophores, fungal-specific antibodies, and sugars. In this review, we provide an overview of the pros and cons of the available radiotracers. We also address the future prospects of fungal-specific imaging.

• Klíčová slova
• PET, immunoPET, invasive fungal infection, radionuclide imaging, siderophores,
• MeSH
• antifungální látky terapeutické užití   MeSH
• invazivní mykotické infekce * MeSH
• lidé MeSH
• mykózy * diagnostické zobrazování   MeSH
• počítačová rentgenová tomografie MeSH
• pozitronová emisní tomografie metody   MeSH
• protilátky fungální MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• antifungální látky MeSH
• protilátky fungální MeSH

Invasive fungal infections such as aspergillosis are life-threatening diseases mainly affecting immuno-compromised patients. The diagnosis of fungal infections is difficult, lacking specificity and sensitivity. This review covers findings on the preclinical use of siderophores for the molecular imaging of infections. Siderophores are low molecular mass chelators produced by bacteria and fungi to scavenge the essential metal iron. Replacing iron in siderophores by radionuclides such as gallium-68 allowed the targeted imaging of infection by positron emission tomography (PET). The proof of principle was the imaging of pulmonary Aspergillus fumigatus infection using [68Ga]Ga-triacetylfusarinine C. Recently, this approach was expanded to imaging of bacterial infections, i.e., with Pseudomonas aeruginosa. Moreover, the conjugation of siderophores and fluorescent dyes enabled the generation of hybrid imaging compounds, allowing the combination of PET and optical imaging. Nevertheless, the high potential of these imaging probes still awaits translation into clinics.

• Klíčová slova
• bacterial, fluorescence, fungal, imaging, infection, positron emission tomography, siderophore,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Pseudomonas aeruginosa is an increasingly prevalent opportunistic pathogen that causes a variety of life-threatening nosocomial infections. Novel strategies for the development of new antibacterial treatments as well as diagnostic tools are needed. One of the novel diagnostic strategies for the detection of infection could be the utilization of siderophores. Siderophores are low-molecular-weight chelators produced by microbes to scavenge essential iron. Replacing iron in siderophores by suitable radiometals, such as Ga-68 for positron emission tomography (PET) imaging, opens approaches for targeted imaging of infection. Here we report on pyoverdine PAO1 (PVD-PAO1), a siderophore produced by P. aeruginosa, labelled with Ga-68 for specific imaging of Pseudomonas infections. PVD-PAO1 was labelled with Ga-68 with high radiochemical purity. The resulting complex showed hydrophilic properties, low protein binding and high stability in human serum. In vitro uptake of 68Ga-PVD-PAO1 was highly dependent on the type of microbial culture. In normal mice 68Ga-PVD-PAO1 showed rapid pharmacokinetics with urinary excretion. PET imaging in infected animals displayed specific accumulation of 68Ga-PVD-PAO1 in infected tissues and better distribution than clinically used 18F-fluorodeoxyglucose (18F-FDG) and 68Ga-citrate. Ga-68 labelled pyoverdine PAO1 seems to be a promising agent for imaging of P. aeruginosa infections by means of PET.

• MeSH
• biologický transport MeSH
• krysa rodu Rattus MeSH
• kultivační média farmakologie   MeSH
• molekulární struktura MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• oligopeptidy * farmakokinetika   MeSH
• PET/CT metody   MeSH
• pozitronová emisní tomografie metody   MeSH
• pseudomonádové infekce diagnostické zobrazování   MeSH
• Pseudomonas aeruginosa účinky léků   metabolismus   MeSH
• radiofarmaka * farmakokinetika   MeSH
• radioizotopy galia * farmakokinetika   MeSH
• siderofory metabolismus   MeSH
• tkáňová distribuce MeSH
• železo farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Gallium-68 MeSH Prohlížeč
• kultivační média MeSH
• oligopeptidy * MeSH
• pyoverdin MeSH Prohlížeč
• radiofarmaka * MeSH
• radioizotopy galia * MeSH
• siderofory MeSH
• železo MeSH

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.

• Klíčová slova
• Bifunctional chelator, Desferrioxamine, Infection, Siderophores, Triacetylfusarinine C,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH