Pilot Evaluation of S-(3-[¹⁸F]Fluoropropyl)-d-Homocysteine and O-(2-[¹⁸F]Fluoroethyl)-d-Tyrosine as Bacteria-Specific Radiotracers for PET Imaging of Infection

There is currently no ideal radiotracer for imaging bacterial infections. Radiolabelled d-amino acids are promising candidates because they are actively incorporated into the peptidoglycan of the bacterial cell wall, a structural feature which is absent in human cells. This work describes fluorine-18 labelled analogues of d-tyrosine and d-methionine, O-(2-[¹⁸F]fluoroethyl)-d-tyrosine (d-[¹⁸F]FET) and S-(3-[¹⁸F]fluoropropyl)-d-homocysteine (d-[¹⁸F]FPHCys), and their pilot evaluation studies as potential radiotracers for imaging bacterial infection.

d-[¹⁸F]FET and d-[¹⁸F]FPHCys were prepared in classical fluorination-deprotection reactions, and their uptake in Staphylococcus aureus and Pseudomonas aeruginosa was evaluated over 2 h. Heat killed bacteria were used as controls. A clinically-relevant foreign body model of S. aureus infection was established in Balb/c mice, as well as a sterile foreign body to mimic inflammation. The ex vivo biodistribution of d-[¹⁸F]FPHCys in the infected and inflamed mice was evaluated after 1 h, by dissection and gamma counting. The uptake was compared to that of [¹⁸F]FDG.

In vitro uptake of both d-[¹⁸F]FET and d-[¹⁸F]FPHCys was specific to live bacteria. Uptake was higher in S. aureus than in P. aeruginosa for both radiotracers, and of the two, higher for d-[¹⁸F]FPHCys than d-[¹⁸F]FET. Blocking experiments with non-radioactive d-[¹⁹F]FPHCys confirmed specificity of uptake. In vivo, d-[¹⁸F]FPHCys had greater accumulation in S. aureus infection compared with sterile inflammation, which was statistically significant. As anticipated, [¹⁸F]FDG showed no significant difference in uptake between infection and inflammation.

d-[¹⁸F]FPHCys uptake was higher in infected tissues than inflammation, and represents a fluorine-18 labelled d-AA with potential to detect a S. aureus reference strain (Xen29) in vivo. Additional studies are needed to evaluate uptake of this radiotracer in clinical isolates.