New insights into radiolabelled siderophores for molecular imaging of bacterial infections

. 2025 Nov 26 ; 3 (1) : 63. [epub] 20251126

Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid41299021

Grantová podpora
IGA LF IGA_LF_2025_006 the Internal Grant Agency of Palacký University
EATRIS-CZ LM2023053 the Ministry of Education, Youth and Sports of the Czech Republic
Programme EXCELES, ID project no. LX22NPO5103 the Ministry of Education, Youth and Sports of the Czech Republic
grant number 24-14579L the Czech Science Foundation

Odkazy

PubMed 41299021
PubMed Central PMC12658088
DOI 10.1038/s44303-025-00126-7
PII: 10.1038/s44303-025-00126-7
Knihovny.cz E-zdroje

This perspective article aims to provide an update on current trends in the research of radiolabelled siderophores for molecular imaging of bacterial infections. It begins by explaining the importance of developing novel diagnostic tools for infections and addresses the limitations of contemporary methods, including molecular imaging. The discussion then shifts to compounds currently being studied for nuclear imaging, with a focus on radiolabelled siderophores and recent advances in their development. It also provides the latest insights into the structures of siderophores, their utilisation by bacteria and their role in bacterial metabolism, as well as potential for labelling with various radioisotopes. Additionally, it presents the use of radiolabelled siderophores, both naturally occurring and artificial siderophore derivates, for imaging of various bacterial infections.

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GBD 2019 Diseases and Injuries Collaborators Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. PubMed DOI PMC

GBD 2019 Antimicrobial Resistance Collaborators Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019. PubMed DOI PMC

O’Neill, J. Antimicrobial resistance: tackling a crisis for the health and wealth of nations. in

Llor, C. & Bjerrum, L. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. PubMed PMC

Cals, J. W. L., Butler, C. C., Hopstaken, R. M., Hood, K. & Dinant, G. J. Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial. PubMed DOI PMC

Sy, R., Rothman, R. E. & Yang, S. PCR-based diagnostics for infectious diseases: uses, limitations, and future applications in acute-care settings. PubMed DOI PMC

Loderstädt, U., Hagen, R. M., Hahn, A. & Frickmann, H. New developments in PCR-based diagnostics for bacterial pathogens causing gastrointestinal infections—a narrative mini-review on challenges in the tropics. PubMed PMC

Eldin, C., Parola, P. & Raoult, D. Limitations of diagnostic tests for bacterial infections. PubMed DOI

FIGDOR, D. & GULABIVALA, K. Survival against the odds: microbiology of root canals associated with post-treatment disease.

Rothe, K. et al. Evaluation of a multiplex PCR screening approach to identify community-acquired bacterial co-infections in COVID-19: a multicenter prospective cohort study of the German competence network of community-acquired pneumonia (CAPNETZ). PubMed DOI PMC

Singh, S. B. et al. Is imaging bacteria with PET a realistic option or an illusion? PubMed PMC

Diaz, L. A. et al. Imaging of musculoskeletal bacterial infections by [ PubMed PMC

Berton, D. C., Kalil, A. C. & Teixeira, P. J. Z. Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator-associated Pneumonia. PubMed PMC

Zhuang, H. & Alavi, A. 18-fluorodeoxyglucose positron emission tomographic imaging in the detection and monitoring of infection and inflammation. PubMed DOI

Lavender, J. P., Lowe, J., Barker, J. R., Burn, J. I. & Chaudhri, M. A. Gallium 67 citrate scanning in neoplastic and inflammatory lesions. PubMed DOI

Littenberg, R. L. et al. Gallium-67 for localization of septic lesions. PubMed DOI

Culverwell, A. D., Scarsbrook, A. F. & Chowdhury, F. U. False-positive uptake on 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) in oncological imaging. PubMed DOI

De Vries, E. F. J., Roca, M., Jamar, F., Israel, O. & Signore, A. Guidelines for the labelling of leucocytes with 99mTc-HMPAO. PubMed PMC

Sarrazin, J.-F., Philippon, F., Trottier, M. & Tessier, M. Role of radionuclide imaging for diagnosis of device and prosthetic valve infections. PubMed DOI PMC

Ordonez, A. A. & Jain, S. K. Pathogen-specific bacterial imaging in nuclear medicine. PubMed PMC

Lai, J., Wang, B., Petrik, M., Beziere, N. & Hammoud, D. A. Radiotracer development for fungal-specific imaging: past, present, and future. PubMed DOI PMC

Davidson, C. Q., Phenix, C. P., Tai, T. C., Khaper, N. & Lees, S. J. Searching for novel PET radiotracers: imaging cardiac perfusion, metabolism and inflammation. PubMed PMC

Rubin, R. H. et al. Radiolabeled, nonspecific, polyclonal human immunoglobulin. PubMed

Malpani, B. L., Kadival, G. V. & Samuel, A. M. Radioimmunoscintigraphic approach for the in vivo detection of tuberculomas-a preliminary study in a rabbit model. PubMed DOI

Sierra, J. M. et al. Accumulation of 99mTc-ciprofloxacin in Staphylococcus aureus and Pseudomonas aeruginosa. PubMed DOI PMC

Sellmyer, M. A. et al. Bacterial infection imaging with [ PubMed DOI PMC

Spoelstra, G. B. et al. Synthesis and preclinical evaluation of novel PubMed DOI PMC

Welling, M. M. et al. Radiochemical and biological characteristics of PubMed DOI

Sarda-Mantel, L. et al. Evaluation of PubMed DOI

Akhtar, M. S., Imran, M. B., Nadeem, M. A. & Shahid, A. Antimicrobial peptides as infection imaging agents: better than radiolabeled antibiotics. PubMed PMC

Baldoni, D. et al. Evaluation of a novel Tc-99m labelled vitamin B12 derivative for targeting Escherichia coli and Staphylococcus aureus in vitro and in an experimental foreign-body infection model. PubMed DOI PMC

Lazzeri, E. et al. Scintigraphic imaging of vertebral osteomyelitis with 111 in-biotin. PubMed

Chen, L. et al. PubMed DOI PMC

Ferreira, I. M. et al. Detection of bacterial infection by a technetium-99m-labeled peptidoglycan aptamer. PubMed DOI

Rusckowski, M., Gupta, S., Liu, G., Dou, S. & Hnatowich, D. J. Investigation of four PubMed DOI PMC

Weinstein, E. A. et al. Imaging enterobacteriaceae infection in vivo with PubMed PMC

Gowrishankar, G. et al. Investigation of 6-[ PubMed PMC

Pullambhatla, M. et al. PubMed PMC

Petrik, M. et al. In vitro and in vivo evaluation of selected PubMed DOI PMC

van Oosten, M. et al. Targeted imaging of bacterial infections: advances, hurdles and hopes. PubMed DOI

Martínez, M. E. et al. New radiosynthesis of 2-deoxy-2-[ PubMed DOI

Neumann, K. D. et al. Imaging active infection in vivo using D-amino acid derived PET radiotracers. PubMed PMC

Lee, S. H. et al. Imaging the bacterial cell wall using N-acetyl muramic acid-derived positron emission tomography radiotracers. PubMed DOI PMC

Chandra, R., Plerno, C. & Braunstein, P. PubMed DOI

Petrik, M. et al. PubMed DOI PMC

Petrik, M. et al. Preclinical evaluation of two PubMed DOI PMC

Petrik, M. et al. In vitro and in vivo comparison of selected Ga-68 and Zr-89 labelled siderophores. PubMed DOI PMC

Petrik, M. et al. Imaging of Pseudomonas Aeruginosa infection with Ga-68 labelled pyoverdine for positron emission tomography. PubMed DOI PMC

Petrik, M. et al. 68Ga-labelled desferrioxamine-b for bacterial infection imaging. PubMed DOI PMC

Bendova, K. et al. [ PubMed DOI PMC

Akter, A. et al. [ PubMed DOI PMC

Petrik, M., Zhai, C., Haas, H. & Decristoforo, C. Siderophores for molecular imaging applications. PubMed DOI PMC

Petrik, M., Pfister, J., Misslinger, M., Decristoforo, C. & Haas, H. Siderophore-based molecular imaging of fungal and bacterial infections—current status and future perspectives. PubMed PMC

Litwin, C. M. & Calderwood, S. B. Role of iron in regulation of virulence genes. PubMed DOI PMC

Page, M. G. P. The role of iron and siderophores in infection, and the development of siderophore antibiotics. PubMed DOI PMC

Wilson, B. R., Bogdan, A. R., Miyazawa, M., Hashimoto, K. & Tsuji, Y. Siderophores in iron metabolism: from mechanism to therapy potential. PubMed DOI PMC

Kronstad, J. W. & Caza, M. Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans. PubMed PMC

Krewulak, K. D. & Vogel, H. J. Structural biology of bacterial iron uptake. PubMed DOI

He, R. et al. SIDERITE: unveiling hidden siderophore diversity in the chemical space through digital exploration. PubMed PMC

Timofeeva, A. M., Galyamova, M. R. & Sedykh, S. E. Bacterial siderophores: classification, biosynthesis, perspectives of use in agriculture. PubMed PMC

Krasulova, K. et al. Preclinical characterisation of gallium-68 labeled ferrichrome siderophore stereoisomers for PET imaging applications. PubMed PMC

Barry, S. M. & Challis, G. L. Recent advances in siderophore biosynthesis. PubMed DOI

Zhou, Z., Lai, J. R. & Walsh, C. T. Directed evolution of aryl carrier proteins in the enterobactin synthetase. PubMed PMC

Patel, P., Song, L. & Challis, G. L. Distinct extracytoplasmic siderophore binding proteins recognize ferrioxamines and ferricoelichelin in Streptomyces coelicolor A3(2). PubMed DOI

Puja, H., Mislin, G. L. A. & Rigouin, C. Engineering siderophore biosynthesis and regulation pathways to increase diversity and availability. PubMed PMC

Klebba, P. E. et al. Iron acquisition systems of Gram-negative bacterial pathogens define TonB-dependent pathways to novel antibiotics. PubMed DOI PMC

Vijay, K., Shibasini, M., Sivasakthivelan, P. & Kavitha, T. Microbial siderophores as molecular shuttles for metal cations: sources, sinks and application perspectives. PubMed

Chao, A., Sieminski, P. J., Owens, C. P. & Goulding, C. W. Iron acquisition in Mycobacterium tuberculosis. PubMed DOI PMC

Rocha, E. R. & Krykunivsky, A. S. Anaerobic utilization of Fe(III)-xenosiderophores among bacteroides species and the distinct assimilation of Fe(III)-ferrichrome by bacteroides fragilis within the genus. PubMed PMC

Chan, D. C. K. & Burrows, L. L. Pseudomonas Aeruginosa FpvB is a high-affinity transporter for xenosiderophores ferrichrome and ferrioxamine B. PubMed PMC

Hussein, S. M., Sofoluwe, A., Paleja, A. & Duhme-Klair, A., Thomas, M. S. Identification of a system for hydroxamate xenosiderophore mediated iron transport in Burkholderia Cenocepacia. PubMed PMC

Lange, M. D. et al. Proteome analysis of virulent Aeromonas hydrophila reveals the upregulation of iron acquisition systems in the presence of a xenosiderophore. PubMed

Kumar, R., Singh, A., & Srivastava, A. Xenosiderophores: bridging the gap in microbial iron acquisition strategies. PubMed

Endicott, N. P., Rivera, G. S. M., Yang, J. & Wencewicz, T. A. Emergence of ferrichelatase activity in a siderophore-binding protein supports an iron shuttle in bacteria. PubMed DOI PMC

Karpowich, N. et al. Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase Active Site of an ABC Transporter. PubMed DOI

Klebba, P. E. ROSET model of tonB action in gram-negative bacterial iron acquisition. PubMed DOI PMC

Schalk, I. J. & Guillon, L. Fate of ferrisiderophores after import across bacterial outer membranes: different iron release strategies are observed in the cytoplasm or periplasm depending on the siderophore pathways. PubMed DOI

Chu, B. C. H. & Vogel, H. J. A structural and functional analysis of type III periplasmic and substrate binding proteins: their role in bacterial siderophore and heme transport. PubMed

Delepelaire, P. Bacterial ABC transporters of iron containing compounds. PubMed DOI

Emery, T. & Hoffer, P. B. Siderophore-mediated mechanism of gallium uptake demonstrated in the microorganism Ustilago sphaerogena. PubMed

Moerlein, S. M., Welch, M. J., Raymond, K. N. & Weitl, F. L. Tricatecholamide analogs of enterobactin as gallium-and indium-binding radiopharmaceuticals. PubMed

Thakur, M. L. Gallium-67 and Indium-111 radiopharmaceuticals. PubMed DOI

Manapragada, P. et al. Gallium 67 SPECT as a treatment monitoring tool in temporal bone and skull base osteomyelitis.

Johnson, H., John, J., Benjamin, J. & Hephzibah, J. A comparative case study between gallium-67 citrate scintigraphy and gallium-68 citrate positron emission tomography-computed tomography in bone infection. PubMed DOI PMC

Dvorakova Bendova, K. et al. Positron emission tomography imaging of Acinetobacter baumannii infection: comparison of gallium-68 labeled siderophores. PubMed DOI PMC

Carter, L. M. et al. The Impact of positron range on PET resolution, evaluated with phantoms and PHITS Monte Carlo simulations for conventional and non-conventional radionuclides. PubMed DOI PMC

Gavriilidis, P., Koole, M., Annunziata, S., Mottaghy, F. M. & Wierts, R. Positron range corrections and denoising techniques for gallium-68 PET imaging: a literature review. PubMed PMC

Kleynhans, J., Ebenhan, T. & Sathekge, M. M. Expanding role for gallium-68 PET imaging in oncology. PubMed DOI

De Feo, M. S. et al. DOI

Takeuchi, Y. et al. Synthesis of acinetobactin. PubMed DOI

Ankenbauer, R. G., Toyokuni, T., Staley, A., Rinehart, K. L. & Cox, C. D. Synthesis and biological activity of pyochelin, a siderophore of Pseudomonas aeruginosa. PubMed DOI PMC

Fuhrmann, J. J. Purification of siderophores from cultures of fluorescent pseudomonas spp by ion-exchange chromatography. DOI

Penwell, W. F. & Actis, L. A. Isolation and characterization of the acinetobactin and baumannoferrin siderophores produced by Acinetobacter baumannii. PubMed

Neilands, J. B. Methodology of Siderophores. in

Garzón-Posse, F., Quevedo-Acosta, Y., Mahecha-Mahecha, C. & Acosta-Guzmán, P. Recent progress in the synthesis of naturally occurring siderophores. DOI

Soares, E. V. Perspective on the biotechnological production of bacterial siderophores and their use. PubMed DOI

Ullah, I. & Lang, M. Key players in the regulation of iron homeostasis at the host-pathogen interface. PubMed PMC

Siddiqui, N. A.; et al. Leveraging copper import by yersiniabactin siderophore system for targeted PET imaging of bacteria. PubMed PMC

Ioppolo, J. A. et al. PubMed DOI

Margeta, R. et al. A novel radiolabelled salmochelin derivative for bacteria-specific PET imaging: synthesis, radiolabelling and evaluation. PubMed DOI

Jiang, Y. et al. Radiolabeling and evaluation of a novel [99mTcN]2+ complex with deferoxamine dithiocarbamate as a potential agent for bacterial infection imaging. PubMed

Mular, A. et al. Cyclic analogs of desferrioxamine E siderophore for PubMed DOI PMC

Mular, A. et al. Biomimetic analogues of the desferrioxamine e siderophore for PET imaging of invasive aspergillosis: targeting properties and species specificity. PubMed DOI PMC

Peukert, C. et al. Optimization of artificial siderophores as 68ga-complexed pet tracers for in vivo imaging of bacterial infections. PubMed DOI

Rayner, B., Verderosa, A. D., Ferro, V. & Blaskovich, M. A. T. Siderophore conjugates to combat antibiotic-resistant bacteria. PubMed DOI PMC

Ferreira, K. et al. Multivalente siderophor-DOTAM-konjugate als Theranostika zur Visualisierung und Behandlung bakterieller Infektionen. DOI

Pandey, A. et al. Theranostic gallium siderophore ciprofloxacin conjugate with broad spectrum antibiotic potency. PubMed DOI PMC

Pandey, A., Śmiłowicz, D. & Boros, E. Galbofloxacin: a xenometal-antibiotic with potentin vitroandin vivoefficacy againstS. Aureus. PubMed DOI PMC

Sanderson, T. J. et al. A Salmochelin S4-inspired ciprofloxacin Trojan horse conjugate. PubMed DOI

Ohmomo, Y. et al. PubMed DOI

Ohmomo, Y. et al. Deferoxamine, a promising bifunctional chelating agent for labeling proteins with gallium: Ga-67 DF-HSA: concise communication. PubMed

Koizumi, M. et al. 67Ga-Labeled antibodies for immunoscintigraphy and evaluation of tumor of drug-antibody conjugates in mice. PubMed

Vosjan, M. J. W. D. et al. Facile labelling of an anti-epidermal growth factor receptor nanobody with 68Ga via a novel bifunctional desferal chelate for immuno-PET. PubMed DOI PMC

Wang, S., Lee, R. J., Mathias, C. J., Green, M. A. & Low, P. S. Synthesis, purification, and tumor cell uptake of 67 Ga-deferoxamine-folate, a potential radiopharmaceutical for tumor imaging. PubMed DOI

Smith-Jones, P. M. et al. Gallium-67/gallium-68-[DFO]-octreotide - a potential radiopharmaceutical for PET imaging of somatostatin receptor-positive tumors: synthesis and radiolabeling in vitro and preliminary in vivo studies. PubMed

Kaeopookum, P. et al. Comparison of 68Ga-labeled rgd mono- and multimers based on a clickable siderophore-based scaffold. PubMed

Zhai, C. et al. Comparison of Ga-68-labeled fusarinine C-based multivalent RGD conjugates and [68Ga]NODAGA-RGD—in vivo imaging studies in human xenograft tumors. PubMed DOI PMC

Zhai, C. et al. Rational design, synthesis and preliminary evaluation of novel fusarinine C-based chelators for radiolabeling with zirconium-89. PubMed PMC

Summer, D. et al. Multimerization results in formation of re-bindable metabolites: a proof of concept study with FSC-based minigastrin imaging probes targeting CCK2R expression. PubMed PMC

Summer, D. et al. Exploiting the concept of multivalency with 68Ga- and 89Zr-labelled fusarinine C-minigastrin bioconjugates for targeting CCK2R expression. PubMed PMC

Wei, W. et al. ImmunoPET: concept, design, and applications. PubMed DOI PMC

Summer, D. et al. Hybrid imaging agents for pretargeting applications based on fusarinine C- proof of concept. PubMed PMC

Gariglio, G. et al. Comparison of two chelator scaffolds as basis for cholecystokinin-2 receptor targeting bimodal imaging probes. PubMed PMC

Koller, A. J. et al. “Off-label use” of the siderophore enterobactin enables targeted imaging of cancer with radioactive Ti(IV). PubMed PMC

Pfister, J. et al. Hybrid imaging of Aspergillus fumigatus pulmonary infection with fluorescent, 68Ga-labelled siderophores. PubMed PMC

Kaeopookum, P. et al. Modifying the siderophore triacetylfusarinine C for molecular imaging of fungal infection. PubMed DOI PMC

Pfister, J. et al. Siderophore Scaffold as carrier for antifungal peptides in therapy of Aspergillus Fumigatus infections. PubMed DOI PMC

Pfister, J. et al. Antifungal siderophore conjugates for theranostic applications in invasive pulmonary aspergillosis using low-molecular tafc scaffolds. PubMed PMC

Misslinger, M. et al. Desferrioxamine B-mediated pre-clinical in vivo imaging of infection by the mold fungus Aspergillus fumigatus. PubMed PMC

Dadachova, E. Future vistas in alpha therapy of infectious diseases. PubMed DOI PMC

Davidov, Y., Tejman-Yarden, N., Robinson, A., Rahav, G. & Nissan, I. Enterobactin and salmochelin s4 inhibit the growth of Staphylococcus aureus. PubMed PMC

Akter, A. et al. Radiotracers for in situ infection imaging: experimental considerations for in vitro microbial uptake of gallium-68-labeled siderophores. PubMed PMC

Winkelmann, G. & Drechsel, H. Microbial siderophores. in

Zhu, W. et al. Xenosiderophore utilization promotes bacteroides thetaiotaomicron resilience during colitis. PubMed DOI PMC

Perry, R. D. & Fetherston, J. D. Yersiniabactin iron uptake: mechanisms and role in yersinia pestis pathogenesis. PubMed DOI PMC

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