Dynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs.

ABSTRACT: Tuberculosis (TB) remains a leading cause of death, but antibiotic treatments for tuberculous meningitis, the deadliest form of TB, are based on those developed for pulmonary TB and not optimized for brain penetration. Here, we perform first-in-human dynamic ¹⁸F-pretomanid positron emission tomography (PET) in eight human subjects to visualize ¹⁸F-pretomanid biodistribution as concentration-time exposures in multiple compartments (NCT05609552), demonstrating preferential brain versus lung tissue partitioning. Preferential, antibiotic-specific partitioning into brain or lung tissues of several antibiotics, active against multidrug resistant (MDR) Mycobacterium tuberculosis strains, are confirmed in experimentally-infected mice and rabbits, using dynamic PET with chemic

SUBMITTER: Chen X 

PROVIDER: S-EPMC11324906 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature