No abstract

Clinical diagnostic tools requiring direct sample testing cannot be applied to infections deep within the body, and clinically available imaging tools lack specificity. New approaches are needed for early diagnosis and monitoring of bacterial infections and rapid detection of drug-resistant organisms. Molecular imaging allows for longitudinal, noninvasive assessments and can provide key information about infectious processes deep within the body.

Oxazolidinones are a novel class of antibacterials with excellent activity against resistant Gram-positive bacteria including strains causing multidrug-resistant tuberculosis (TB). Despite their excellent efficacy, optimal dosing strategies to limit their toxicities are still under development. Here, we developed a novel synthetic strategy for fluorine-18-radiolabeled oxazolidinones. As proof-of-concept, we performed whole-body 18 Flinezolid positron emission tomography (PET) in a mouse model of pulmonary TB for noninvasive in situ measurements of time−activity curves in multiple compartments with subsequent confirmation by ex vivo tissue gamma counting. After intravenous injection, 18 F-linezolid rapidly distributed to all organs with excellent penetration into Mycobacterium tuberculosis-infected lungs. Drug biodistribution studies with PET can provide unbiased, in situ drug measurements, which could boost efforts to optimize antibiotic dosing strategies.