Artificial Siderophore Modification and Metal Coordination Providing Selectivity for Imaging of Bacterial Infections
Abstract
Purpose: diagnosing bacterial infections can be challenging, as the source of infection is often difficult to identify. Positron emission tomography (PET) imaging with bacteriaspecific agents offers a promising approach to localizing and potentially characterizing infection sites. In this study, we compared the selectivity of two iron chelators, the natural siderophore FOX E and its synthetic variant FOX 2-5, for targeting different pathogens when radiolabeled for molecular imaging. Methods: Both siderophores were evaluated across various bacteria, including Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, and Escherichia coli. The siderophores were labeled with radioactive gallium-68 and iron-59 for short-term uptake assays. In addition, 68 Ga-labeled siderophores were applied in a murine infection model of the respective pathogens for PET imaging. Results: Our in vitro results demonstrated that both siderophores were taken up by bacteria when labeled with iron-59. However, when labeled with gallium-68, FOX 2-5 exhibited strain-specific differences: while gallium-68 uptake was similar for both chelators in S. aureus and A. baumannii, FOX 2-5 failed to accumulate in P. aeruginosa and K. pneumoniae unlike FOX E. These findings were confirmed in vivo with corresponding differences in the PET images of mouse infection models. Conclusion: minor modifications in the structure of siderophores can alter bacterial specificity, particularly when coordinated with gallium. Additionally, this study revealed a distinction in recognition between gallium and iron complexes in the Gram-negative P. aeruginosa and K. pneumoniae. These findings highlight artificial siderophores as versatile, customizable agents for characterizing and potentially diagnosing bacterial infections.
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BibTeX
@article{knoll2026artificial,
title = {{Artificial Siderophore Modification and Metal Coordination Providing Selectivity for Imaging of Bacterial Infections}},
author = {Adriana Knoll and Kateřina Dvořáková Bendová and Isidor Happacher and Barbora Neužilová and Beate Abt and Isabelle J. Schalk and Elzbieta Gumienna-Kontecka and Hubertus Haas and Miloš Petřík and Clemens Decristoforo},
journal = {Chemical \& Biomedical Imaging},
year = {2026},
month = sep,
doi = {10.1021/cbmi.6c00132},
url = {https://hal.science/hal-05735724v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Artificial Siderophore Modification and Metal Coordination Providing Selectivity for Imaging of Bacterial Infections
AU - Adriana Knoll
AU - Kateřina Dvořáková Bendová
AU - Isidor Happacher
AU - Barbora Neužilová
AU - Beate Abt
AU - Isabelle J. Schalk
AU - Elzbieta Gumienna-Kontecka
AU - Hubertus Haas
AU - Miloš Petřík
AU - Clemens Decristoforo
PY - 2026
DA - 2026/09/02
JO - Chemical & Biomedical Imaging
DO - 10.1021/cbmi.6c00132
UR - https://hal.science/hal-05735724v1
AB - Purpose: diagnosing bacterial infections can be challenging, as the source of infection is often difficult to identify. Positron emission tomography (PET) imaging with bacteriaspecific agents offers a promising approach to localizing and potentially characterizing infection sites. In this study, we compared the selectivity of two iron chelators, the natural siderophore FOX E and its synthetic variant FOX 2-5, for targeting different pathogens when radiolabeled for molecular imaging. Methods: Both siderophores were evaluated across various bacteria, including Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, and Escherichia coli. The siderophores were labeled with radioactive gallium-68 and iron-59 for short-term uptake assays. In addition, 68 Ga-labeled siderophores were applied in a murine infection model of the respective pathogens for PET imaging. Results: Our in vitro results demonstrated that both siderophores were taken up by bacteria when labeled with iron-59. However, when labeled with gallium-68, FOX 2-5 exhibited strain-specific differences: while gallium-68 uptake was similar for both chelators in S. aureus and A. baumannii, FOX 2-5 failed to accumulate in P. aeruginosa and K. pneumoniae unlike FOX E. These findings were confirmed in vivo with corresponding differences in the PET images of mouse infection models. Conclusion: minor modifications in the structure of siderophores can alter bacterial specificity, particularly when coordinated with gallium. Additionally, this study revealed a distinction in recognition between gallium and iron complexes in the Gram-negative P. aeruginosa and K. pneumoniae. These findings highlight artificial siderophores as versatile, customizable agents for characterizing and potentially diagnosing bacterial infections.
SN - 2832-3637
ER -