Siderophore-Based Molecular Imaging of Fungal and Bacterial Infections-Current Status and Future Perspectives.

Milos Petrik,Matthias Misslinger,Joachim Pfister,Clemens Decristoforo,Hubertus Haas

doi:10.3390/jof6020073

Milos Petrik, Matthias Misslinger + Show 3 more

Open Access

https://doi.org/10.3390/jof6020073

Copy DOI

Abstract

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.

Highlights

Iron is an indispensable metal for virtually all organisms
The presence of SITs species that lack the production of siderophores, such as Saccharomyces cerevisiae, Candida albicans, is confined to the fungal kingdom and even species that lack the production of siderophores, or such
We concluded that 68 Ga-labeled siderophores, in particular [68 Ga]Ga-triacetylfusarinine C (TAFC), have a high potential as radiotracers to image invasive A. fumigatus infections in patients

Summary

Introduction

Iron is an indispensable metal for virtually all organisms. During infection, pathogens typically encounter iron limitation as the host iron is tightly sequestered by host proteins such as hemoglobin, transferrin, lactoferrin, and ferritin and iron–sulfur cluster proteins [1]. Transporter (SIT) belong subfamily of the major the siderophore-iron complex up by specific transporter, which to the Siderophore facilitator protein superfamily [6]. The presence of SITs species that lack the production of siderophores, such as Saccharomyces cerevisiae, Candida albicans, is confined to the fungal kingdom and even species that lack the production of siderophores, or such. Within the TAFC and FsC[9,10,11]; are hydrolyzed by iron specific esterases [9,10,11]; thethe metabolism or can be stored either in the intracellular siderophore ferricrocin or within the released iron is transferred to the metabolism or can be stored either in the intracellular siderophore vacuole [12]. These differences enable fungalMoreover, bacteria and mammals lack SIT-type transporters [6] These differences enable fungal-specific specific in vivo targeting strategies exploiting the siderophore system.

Concept

Siderophore Modifications

67 Ga-labeling and included modifications to adjust pharmacokinetics for imaging

Siderophore

Conclusions and Outlook