Determination of [11C]Rifampin Pharmacokinetics within Mycobacterium tuberculosis-Infected Mice by Using Dynamic Positron Emission Tomography Bioimaging

摘要: ABSTRACT Information about intralesional pharmacokinetics (PK) and spatial distribution of tuberculosis (TB) drugs is limited has not been used to optimize dosing recommendations for new or existing drugs. While techniques can detect their metabolites within TB granulomas, they are invasive, rely on accurate resection tissues, do capture dynamic drug in the tissues interest. In this study, we assessed situ 11 C-labeled rifampin live, Mycobacterium tuberculosis-infected mice that develop necrotic lesions akin human disease. Dynamic positron emission tomography (PET) imaging was performed over 60 min after injection [ C]rifampin as a microdose, standardized uptake values (SUV) were calculated, noncompartmental analysis estimate PK parameters compartments rapidly distributed all parts body quickly localized liver. Areas under concentration-time curve first (AUC 0–60 ) infected uninfected similar liver, blood, brain ( P > 0.53) uniformly low (10 20% blood values). However, lower concentrations noted lung than healthy lungs = 0.03). Ex vivo two-dimensional matrix-assisted laser desorption ionization (MALDI) confirmed restricted penetration into lesions. Noninvasive bioimaging be assess interest, with potential applications regimen development.