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

Filipa Mota, Ravindra Jadhav, Camilo A. Ruiz-Bedoya, Alvaro A. Ordonez, Mariah H. Klunk, Joel S. Freundlich, Sanjay K. Jain

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)916-921
Number of pages6
JournalACS Infectious Diseases
Volume6
Issue number5
DOIs
StatePublished - May 8 2020

Keywords

  • fluoride-18
  • PET
  • pharmacokinetics
  • tuberculosis

ASJC Scopus subject areas

  • Infectious Diseases

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