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.

PET/CT features of a novel gallium-68 labelled hypoxia seeking agent in patients diagnosed with tuberculosis: a proof-of-concept study.

INTRODUCTION: Positron emission tomography/computed tomography (PET/CT) in infection and inflammation has yielded promising results across a range of radiopharmaceuticals. In particular, PET/CT imaging of tuberculosis (TB) allows for a better understanding of this complex disease by providing insights into molecular processes within the TB microenvironment. TB lesions are hypoxic with research primarily focussed on cellular processes occurring under hypoxic stress. With the development of hypoxia seeking PET/CT radiopharmaceuticals, that can be labelled in-house using a germanium-68/gallium-68 (68Ge/68Ga) generator, a proof-of-concept for imaging hypoxia in TB is presented. METHODS: Ten patients diagnosed with TB underwent whole-body PET/CT imaging, 60-90 min after intravenous administration of 74-185 MBq (2-5 mCi) 68Ga-nitroimidazole. No oral or intravenous contrast was administered. Images were visually and semiquantitatively assessed for abnormal 68Ga-uptake in the lungs. RESULTS: A total of 28 lesions demonstrating hypoxic uptake were identified. Low- to moderate-uptake was seen in nodules, areas of consolidation and cavitation as well as effusions. The mean standard uptake value (SUVmean) of the lesions was 0.47 (IQR, 0.32-0.82) and SUVmax was 0.71 (IQR, 0.41-1.11). The lesion to muscle ratio (median, 1.70; IQR, 1.15-2.31) was higher than both the left ventricular and the aorta lesion to blood ratios. CONCLUSION: Moving towards the development of unique host-directed therapies (HDT), modulation of oxygen levels may improve therapeutic outcome by reprogramming TB lesions to overcome hypoxia. This proof-of-concept study suggests that hypoxia in TB lesions can be imaged and quantified using 68Ga-nitroimidazole PET/CT. Subsequently, hypoxic load can be estimated to inform personalised treatment plans of patients diagnosed with TB.

An overview of the developments and potential applications of 68Ga-labelled PET/CT hypoxia imaging.

Non-invasive imaging of hypoxia plays a role in monitoring the body's adaptive response or the development of pathology under hypoxic conditions. Various techniques to image hypoxia have been investigated with a shift towards the use of molecular imaging using PET/CT. The role of hypoxia-specific radiopharmaceuticals such as radiolabelled nitroimidazoles is well documented particularly in the oncologic setting. With the increasing utilisation of in-house labelling with a PET benchtop generator, such as the 68Ge/68Ga generator, the use of 68Ga-labelled hypoxic radiopharmaceuticals in the clinical setting is developing. Since hypoxia plays a role in various pathologic states including infectious disease such as TB, there is a need to explore the potential application of 68Ga-labelled hypoxia seeking radiopharmaceuticals beyond oncology. The purpose of this review is to describe the developments of 68Ga-labelled hypoxic radiopharmaceuticals including the various chelators that have been investigated. Further, the role of hypoxia imaging in various pathologies is discussed with particular emphasis on the potential clinical applications of hypoxia PET/CT in TB.

A randomized-controlled study of a modified technique to reduce extracardiac activity in myocardial perfusion imaging.

INTRODUCTION: Various techniques have been used in an attempt to reduce interfering extracardiac activity in myocardial perfusion imaging with inconsistent results. The aim of this study was to investigate the effect of a combined intervention on the frequency and intensity of interfering extracardiac activity. METHODS: Patients (n=230) routinely referred for a 2-day stress-rest myocardial perfusion examination were assigned randomly to one of two groups. Group A (n=114) received a single intervention (diluted lemon juice) before stress imaging and a combined intervention (diluted lemon juice and soda water) before rest imaging. Interventions were reversed for group B (n=116). Three interpreters, blinded to the intervention, assessed early and delayed planar images from 195 patients in terms of the frequency and the intensity of interfering extracardiac activity. RESULTS: The myocardial to extracardiac (MYO : EXC) ratio between groups for the rest studies was marginally not significant (P=0.060 and 0.059), showing an increase in ratio when the combined intervention was administered. There were significant differences (P≤0.001) in the frequency, intensity, and MYO : EXC ratio between the early and the delayed studies. CONCLUSION: Combining interventions that stimulate radiopharmaceutical hepatic excretion and utilize the volume effect is advantageous in myocardial perfusion imaging, with delayed imaging being advocated as a complementary intervention.