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[(18)F]FDG-6-P as a novel in vivo tool for imaging staphylococcal infections
Bethany Mills1, Ramla O Awais2, Jeni Luckett3
1School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, University Boulevard, Nottingham, NG7 2RD UK.
Background:
Management of infection is a major clinical problem. Staphylococcus aureus is a Gram-positive bacterium which colonises approximately one third of the adult human population. Staphylococcal infections can be life-threatening and are frequently complicated by multi-antibiotic resistant strains including methicillin-resistant S. aureus (MRSA). Fluorodeoxyglucose ([(18)F]FDG) imaging has been used to identify infection sites; however, it is unable to distinguish between sterile inflammation and bacterial load. We have modified [(18)F]FDG by phosphorylation, producing [(18)F]FDG-6-P to facilitate specific uptake and accumulation by S. aureus through hexose phosphate transporters, which are not present in mammalian cell membranes. This approach leads to the specific uptake of the radiopharmaceutical into the bacteria and not the sites of sterile inflammation.
Methods:
[(18)F]FDG-6-P was synthesised from [(18)F]FDG. Yield, purity and stability were confirmed by RP-HPLC and iTLC. The specificity of [(18)F]FDG-6-P for the bacterial universal hexose phosphate transporter (UHPT) was confirmed with S. aureus and mammalian cell assays in vitro. Whole body biodistribution and accumulation of [(18)F]FDG-6-P at the sites of bioluminescent staphylococcal infection were established in a murine foreign body infection model.
Results:
In vitro validation assays demonstrated that [(18)F]FDG-6-P was stable and specifically transported into S. aureus but not mammalian cells. [(18)F]FDG-6-P was elevated at the sites of S. aureus infection in vivo compared to uninfected controls; however, the increase in signal was not significant and unexpectedly, the whole-body biodistribution of [(18)F]FDG-6-P was similar to that of [(18)F]FDG.
Conclusions:
Despite conclusive in vitro validation, [(18)F]FDG-6-P did not behave as predicted in vivo. However at the site of known infection, [(18)F]FDG-6-P levels were elevated compared with uninfected controls, providing a higher signal-to-noise ratio. The bacterial UHPT can transport hexose phosphates other than glucose, and therefore alternative sugars may show differential biodistribution and provide a means for specific bacterial detection.
Insights
Researchers developed a novel radiopharmaceutical, [(18)F]FDG-6-P, for detecting Staphylococcus aureus infections. While it showed promise in vitro, in vivo results were not as expected, though it did offer improved signal in infected areas.
Area of Science:
- Nuclear medicine
- Infectious disease diagnostics
- Radiopharmaceutical development
Background:
- Staphylococcus aureus infections pose a significant clinical challenge, often complicated by antibiotic resistance.
- Current imaging agents like Fluorodeoxyglucose ([(18)F]FDG) cannot differentiate between sterile inflammation and bacterial infection.
- A novel approach is needed for specific bacterial detection.
Purpose of the Study:
- To develop and evaluate a novel radiopharmaceutical, [(18)F]FDG-6-P, for the specific detection of Staphylococcus aureus infections.
- To assess the in vitro and in vivo performance of [(18)F]FDG-6-P in targeting bacterial hexose phosphate transporters.
Main Methods:
- [(18)F]FDG-6-P was synthesized from [(18)F]FDG and characterized for stability and purity.
- In vitro assays confirmed specific uptake by S. aureus via the universal hexose phosphate transporter (UHPT), with no uptake in mammalian cells.
- In vivo studies in a murine model evaluated the biodistribution and infection site accumulation of [(18)F]FDG-6-P.
Main Results:
- In vitro studies confirmed [(18)F]FDG-6-P stability and specific transport into S. aureus, not mammalian cells.
- In vivo, [(18)F]FDG-6-P showed elevated levels at S. aureus infection sites compared to controls, but the signal increase was not statistically significant.
- Whole-body biodistribution of [(18)F]FDG-6-P in vivo mirrored that of [(18)F]FDG.
Conclusions:
- Despite promising in vitro results, [(18)F]FDG-6-P did not perform as predicted in vivo.
- Elevated [(18)F]FDG-6-P levels at infection sites suggest potential for improved signal-to-noise ratio.
- Exploring alternative sugars for transport via the bacterial UHPT may lead to more effective specific bacterial detection agents.
