68 Ga-nitroimidazole PET/CT imaging of hypoxia in tuberculosis: A case series.

Tuberculosis (TB) lesions in humans have been proven to be severely hypoxic with hypoxia leading to latency and dormancy of disease. Dormant TB lesions become less susceptible to standard TB treatment regimens with varying responses to treatment but may have increased susceptibility to nitroimidazole drugs. This in turn implies that positron emission tomography / computed tomography (PET/CT) imaging with radiolabelled nitroimidazoles may identify patients who will benefit from treatment with antimicrobial agents that are active against anaerobic bacteria. This case series aims to highlight the hypoxic uptake and retention of a novel 68 Ga-labelled hypoxia-seeking agent in TB lesions at different time points during anti-TB therapy using PET/CT imaging. Patients with confirmed TB underwent whole-body PET/CT after administration of a 68 Ga-nitroimidazole derivative at baseline and follow-up. Images were analysed both qualitatively and semi-quantitatively. Hypoxic uptake and change in uptake over time were analysed using lesion-to-muscle ratio (LMR) and lesion-to-blood ratio (LBR). 68 Ga-nitroimidazole avid lesions were demonstrated most frequently in the upper lobes of the lung. Low-grade hypoxic uptake was visualised in areas of consolidation, cavitation, nodules and lymph nodes. From baseline to follow-up imaging, the LMR increased with persistent hypoxic load despite morphologic improvement. This case series highlights the dynamic hypoxic microenvironment in TB lesions. From these initial data, it appears that 68 Ga-nitroimidazole is a promising candidate for monitoring hypoxic load in patients diagnosed with TB. Such imaging could identify patients who would benefit from individualised therapy targeting other mechanisms in the TB microenvironment with the intention to predict or improve treatment response.

Evolution of newer regimens in TB from RNTCP to NTEP.

TB is a global disease and the leading cause of death among infectious diseases worldwide. TB was considered incurable till the mid 19th century. The major landmark in the treatment was the discovery of Rifampicin which has led to shorter courses of therapy as compared to the previous regimens which also consisted of injectables. Although, treatment for TB is evolving expeditiously today but a lot needs to be done as far as drug resistant TB (DRTB) is concerned. Non-standard regimens in private sector, lack of access to drug susceptibility testing, delay in the treatment, poor follow up and default in the treatment has led to emergence DRTB. Addition of newer drugs like bedaquiline and delamanid has made oral regimen possible in DRTB as well. Encouraging results of BPaL regimen for extensively drug resistant TB (XDR-TB) may prove to be a game changer. The target of TB elimination by 2025 is onerous considering the huge population, rising DRTB patients and private sector non engagement in the programme despite implementation of second largest national programme of the world.