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

Area of Science:

• Nuclear medicine
• Radiochemistry
• Infectious disease imaging

Background:

• Conventional methods for imaging infections are challenging.
• Positron emission tomography (PET) radiotracers targeting bacterial metabolism offer a promising alternative.
• Existing peptidoglycan-targeted PET tracers often use short-lived isotopes, limiting their clinical utility.

Purpose of the Study:

• To develop novel PET radiotracers for infection imaging.
• To utilize the longer-lived fluorine-18 isotope for improved PET imaging of bacterial infections.
• To target the amino sugar component of peptidoglycan, specifically N-acetyl muramic acid (NAM).

Main Methods:

• Synthesis of enantiomeric N-acetyl muramic acid (NAM) derivatives labeled with fluorine-18.
• Reaction of muramic acid with 4-nitrophenyl 2-[¹⁸F]fluoropropionate ([¹⁸F]NFP).
• Isolation of diastereomers (S)-[¹⁸F]FMA and (R)-[¹⁸F]FMA.
• In vitro and in vivo evaluation of tracer accumulation in human pathogens.

Main Results:

• Successfully synthesized and isolated both (S)-[¹⁸F]FMA and (R)-[¹⁸F]FMA.
• Demonstrated robust accumulation of the tracers by human pathogens, including Staphylococcus aureus.
• Showed significant accumulation in vitro and in vivo, indicating potential for infection detection.

Conclusions:

• Fluorine-18-labeled NAM-derived PET radiotracers are effective tools for infection imaging.
• These novel tracers offer advantages over existing methods due to the longer half-life of fluorine-18.
• The developed radiotracers provide a foundation for future clinical studies in diagnosing bacterial infections.