Abstract
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 18F-linezolid 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, 18F-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.
Original language | English (US) |
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Pages (from-to) | 916-921 |
Number of pages | 6 |
Journal | ACS Infectious Diseases |
Volume | 6 |
Issue number | 5 |
DOIs | |
State | Published - May 8 2020 |
Keywords
- PET
- fluoride-18
- pharmacokinetics
- tuberculosis
ASJC Scopus subject areas
- Infectious Diseases