Targeted PET Imaging of Pseudomonas aeruginosa Using a [ ⁶⁸ Ga]Ga-Pyoverdines Cocktail

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.