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

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.