Imaging latent tuberculosis infection with radiolabeled nitroimidazoles

Abstract

In a previous paper, an overview of the use of PET/CT in the management of tuberculosis (TB) was provided and the potential role of nitroimidazole imaging in LTBI was considered [1]. During latent TB, dormant bacilli putatively reside in a hypoxic environment of caseating lung granulomas. Exposure of Mycobacterium tuberculosis (Mtb) to progressive hypoxia in vitro induces a dormant state characterized by reduced replication and metabolism analogous to that postulated for bacilli in LTBI. In vitro, Mtb has been shown to enter microaerophilic nonreplicating persistent (NRP) stage 1, if the dissolved oxygen content falls below 1 %. NRP stage 1 is characterized by thickening of the outer cell wall of Mtb and termination of DNA synthesis. If the oxygen content further drops to approximately 0.06 %, the bacilli enter NRP stage 2, which is accompanied by reduced susceptibility to standard anti- TB drugs but increased susceptibility to nitroimidazole drugs [2]. In light of this, metronidazole, an antimicrobial agent active against anaerobic bacteria, has been investigated as a possible therapy for TB, particularly latent and persistent TB. Metronidazole has recently been documented to be a viable option for treatment of multidrugresistant (MDR) TB [3].