Radiosynthesis and Biodistribution of 18F-Linezolid in Mycobacterium tuberculosis-Infected Mice Using Positron Emission Tomography
- 8 April 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Infectious Diseases
- Vol. 6 (5), 916-921
- https://doi.org/10.1021/acsinfecdis.9b00473
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 F-18-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, F-18-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.Funding Information
- National Institutes of Health (R01-EB020539, R56-AI145435)
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