Radiosynthesis and Biodistribution of 18F-Linezolid in Mycobacterium tuberculosis-Infected Mice Using Positron Emission Tomography.

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.

• Authors: Filipa Mota, Ravindra Jadhav, Camilo A Ruiz-Bedoya, Alvaro A Ordonez, Mariah H Klunk, Joel S Freundlich, Sanjay K Jain
• Journal: ACS infectious diseases (ACS Infect Dis) Vol. 6 Issue 5 Pg. 916-921 (05 08 2020) ISSN: 2373-8227 [Electronic] United States
• PMID: 32243132 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Fluorine Radioisotopes
• Fluorine-18
• Linezolid

Topics

• Animals
• Fluorine Radioisotopes
• Linezolid (pharmacokinetics)
• Lung (diagnostic imaging)
• Mice
• Mycobacterium tuberculosis
• Positron-Emission Tomography
• Tissue Distribution
• Tuberculosis, Multidrug-Resistant (drug therapy)