Imaging the Bacterial Cell Wall Using N -Acetyl Muramic Acid-Derived Positron Emission Tomography Radiotracers.

Imaging infections in patients is challenging using conventional methods, motivating the development of positron emission tomography (PET) radiotracers targeting bacteria-specific metabolic pathways. Numerous techniques have focused on the bacterial cell wall, although peptidoglycan-targeted PET tracers have been generally limited to the short-lived carbon-11 radioisotope ( t 1/2 = 20.4 min). In this article, we developed and tested new tools for infection imaging using an amino sugar component of peptidoglycan, namely, derivatives of N -acetyl muramic acid (NAM) labeled with the longer-lived fluorine-18 ( t 1/2 = 109.6 min) radioisotope. Muramic acid was reacted directly with 4-nitrophenyl 2-[ 18 F]fluoropropionate ([ 18 F]NFP) to afford the enantiomeric NAM derivatives ( S )-[ 18 F]FMA and ( R )-[ 18 F]FMA. Both diastereomers were easily isolated and showed robust accumulation by human pathogens in vitro and in vivo, including Staphylococcus aureus . These results form the basis for future clinical studies using fluorine-18-labeled NAM-derived PET radiotracers.