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Published on: April 25, 2025
Targeted PET Imaging of Pseudomonas aeruginosa Using a [68Ga]Ga-Pyoverdines Cocktail
Kristyna Krasulova1, Barbora Neuzilova1, Katerina Dvorakova Bendova1
1Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University, Olomouc, Czech Republic.
Abstract:
Pseudomonas aeruginosa is a major cause of nosocomial infections. Current diagnostic methods often lack sensitivity and specificity, resulting in a delayed or inaccurate diagnosis. To address these limitations, new diagnostic strategies are being developed. Molecular imaging techniques, such as PET, allow localization and monitoring of infections in situ; however, specific radiotracers for P. aeruginosa imaging are lacking. Radiolabeled siderophores have shown promise as diagnostic tools for PET imaging. Pyoverdines, specific siderophores produced by P. aeruginosa, are classified into 3 types: pyoverdine type I (PVDI), pyoverdine type II (PVDII), and pyoverdine type III (PVDIII). In this study, we evaluated a radiotracer specifically targeting P. aeruginosa infections using radiolabeled pyoverdines. Methods: We radiolabeled PVDI, PVDII, and PVDIII with 68Ga and evaluated their stability, in vitro uptake by microbial cultures, and in vivo biodistribution in healthy animals and 2 animal infection models. A cocktail of [68Ga]Ga-PVDI, [68Ga]Ga-PVDII, and [68Ga]Ga-PVDIII was used for PET imaging. Results: The radiolabeled pyoverdines exhibited high in vitro and in vivo stability, rapid renal clearance, and low blood retention. In vitro uptake using reference strains and clinical isolates showed that each strain had high uptake of one specific pyoverdine type. The cocktail successfully detected all tested P. aeruginosa strains in vivo, with no tracer accumulation observed in sterile inflammation, other pathogens, or heat-inactivated bacterial cells, confirming its specificity. Conclusion: A [68Ga]Ga-pyoverdines cocktail was developed as a specific PET imaging agent for detecting P. aeruginosa infections. Combining 3 radiotracers for broad strain coverage represents a significant advance in the accurate diagnosis of P. aeruginosa infections and confirms the potential utility of radiolabeled siderophores in PET imaging of infections.
Insights
A new Gallium-68 labeled pyoverdines cocktail offers a specific PET imaging agent for detecting Pseudomonas aeruginosa infections. This diagnostic tool combines three radiotracers for broad strain coverage, improving accuracy in identifying these common nosocomial infections.
Area of Science:
- Molecular imaging
- Infectious disease diagnostics
- Radiopharmaceutical development
Background:
- Pseudomonas aeruginosa is a significant cause of hospital-acquired infections.
- Current diagnostic methods for P. aeruginosa infections lack sensitivity and specificity, leading to delayed or inaccurate diagnoses.
- Positron Emission Tomography (PET) imaging offers in situ localization and monitoring of infections, but requires specific radiotracers.
Purpose of the Study:
- To develop and evaluate a novel PET imaging agent for specific detection of Pseudomonas aeruginosa infections.
- To investigate the utility of radiolabeled pyoverdines, specific siderophores of P. aeruginosa, as PET imaging agents.
- To assess a cocktail of three radiolabeled pyoverdine types for broad strain coverage and diagnostic accuracy.
Main Methods:
- Pyoverdine type I (PVDI), pyoverdine type II (PVDII), and pyoverdine type III (PVDIII) were radiolabeled with Gallium-68 (68Ga).
- Radiolabeled pyoverdines were evaluated for in vitro stability, microbial uptake, and in vivo biodistribution in healthy and infected animal models.
- A cocktail of [68Ga]Ga-PVDI, [68Ga]Ga-PVDII, and [68Ga]Ga-PVDIII was used for PET imaging of P. aeruginosa infections.
Main Results:
- The radiolabeled pyoverdines demonstrated high in vitro and in vivo stability, rapid renal clearance, and low blood retention.
- In vitro studies showed specific uptake of each pyoverdine type by different P. aeruginosa strains.
- The [68Ga]Ga-pyoverdines cocktail successfully detected all tested P. aeruginosa strains in vivo with high specificity, showing no uptake in sterile inflammation or other pathogens.
Conclusions:
- A Gallium-68 labeled pyoverdines cocktail has been successfully developed as a specific PET imaging agent for P. aeruginosa infections.
- This multi-tracer approach provides broad strain coverage, representing a significant advancement in the accurate diagnosis of P. aeruginosa.
- Radiolabeled siderophores show significant potential as diagnostic tools for PET imaging of bacterial infections.
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