Improved Radiosynthesis of [¹⁸F]-Labeled Oxazolidinone Antibiotics for Future Clinical Translation

The development of radiolabeled antibiotics for positron emission tomography/computed tomography (PET/CT) imaging has the potential to substantially improve our ability to measure compartment-specific antibiotic exposures for various infections. This study focuses on the radiosynthesis and optimization of fluorine-18 [¹⁸F]-labeled oxazolidinone antibiotics, specifically [¹⁸F]linezolid and [¹⁸F]sutezolid, followed by in vivo imaging of the latter. Copper-mediated radiofluorination of boronated precursors was enhanced by variation of the phase-transfer catalysts and base conditions to improve the reaction efficiency. Preclinical evaluation of [¹⁸F]sutezolid in uninfected and Mycobacterium tuberculosis-infected mice demonstrated favorable biodistribution and metabolic stability, with minimal defluorination. Dynamic PET imaging confirmed rapid clearance, predominant renal and hepatobiliary excretion, and consistent tissue uptake across infected and uninfected models. These findings support the feasibility of [¹⁸F]-labeled oxazolidinones as PET tracers for compartment-specific antibiotic exposures, paving the way for optimizing antibiotic dosing and future personalized treatments in patients.