posted on 2023-11-24, 00:34authored bySang Hee Lee, Jung Min Kim, Marina López-Álvarez, Chao Wang, Alexandre M. Sorlin, Kondapa Naidu Bobba, Priamo A. Pichardo-González, Joseph Blecha, Youngho Seo, Robert R. Flavell, Joanne Engel, Michael A. Ohliger, David M. Wilson
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 (t1/2 = 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 (t1/2 = 109.6 min) radioisotope. Muramic acid was reacted directly
with 4-nitrophenyl 2-[18F]fluoropropionate ([18F]NFP) to afford the enantiomeric NAM derivatives (S)-[18F]FMA and (R)-[18F]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.