title: [(18)F]FDG-6-P as a novel in vivo tool for imaging staphylococcal infections.
abstract: 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.
authors: School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, University Boulevard, Nottingham, NG7 2RD UK.
authors: Bethany
authors: B
authors: Mills
authors: School of Medicine, University of Nottingham, Nottingham, NG7 2RD UK.
authors: Ramla O
authors: RO
authors: Awais
authors: School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, University Boulevard, Nottingham, NG7 2RD UK ; School of Medicine, University of Nottingham, Nottingham, NG7 2RD UK.
authors: Jeni
authors: J
authors: Luckett
authors: PETNET Solutions, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1 PB UK.
authors: Dave
authors: D
authors: Turton
authors: School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, University Boulevard, Nottingham, NG7 2RD UK.
authors: Paul
authors: P
authors: Williams
authors: School of Medicine, University of Nottingham, Nottingham, NG7 2RD UK.
authors: Alan C
authors: AC
authors: Perkins
authors: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, LE12 5RD UK.
authors: Philip J
authors: PJ
authors: Hill
keywords: Infection diagnosis; NanoPET-CT imaging; Pre-clinical; S. aureus