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

Betts, Helen M.; Luckett, Jeni C.; Hill, Philip J.

Abstract

Purpose 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. Procedures 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. Results 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. Conclusions 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.

Citation

Betts, H. M., Luckett, J. C., & Hill, P. J. (2024). 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. Molecular Imaging and Biology, 26, 704-713. https://doi.org/10.1007/s11307-024-01929-7

• Journal Article Type: Article
• Acceptance Date: Jun 14, 2024
• Online Publication Date: Jun 28, 2024
• Publication Date: 2024-08
• Deposit Date: Jul 4, 2024
• Publicly Available Date: Jul 4, 2024
• Journal: Molecular Imaging and Biology
• Print ISSN: 1536-1632
• Electronic ISSN: 1860-2002
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Pages: 704-713
• DOI: https://doi.org/10.1007/s11307-024-01929-7
• Public URL: https://nottingham-repository.worktribe.com/output/36579526
• Publisher URL: https://link.springer.com/article/10.1007/s11307-024-01929-7
• Additional Information: Received: 5 February 2024; Revised: 12 June 2024; Accepted: 14 June 2024; First Online: 28 June 2024; : ; : The authors declare that they have no conflict of interest.