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-[F-18]fluoropropionate ([F-18]NFP) to afford the enantiomeric NAM derivatives (S)-[F-18]FMA and (R)-[F-18]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.