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

Abstract

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 ( 68 Ge/ 68 Ga) 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) 68 Ga-nitroimidazole. No oral or intravenous contrast was administered. Images were visually and semiquantitatively assessed for abnormal 68 Ga-uptake in the lungs. ResultsA 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 (SUV mean ) of the lesions was 0.47 (IQR, 0.32-0.82) and SUV max 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. ConclusionMoving 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 68 Ga-nitroimidazole PET/CT. Subsequently, hypoxic load can be estimated to inform personalised treatment plans of patients diagnosed with TB.

Molecular Imaging of Tuberculosis

“…145 More recently, the potential of 68 Ganitroimidazole for hypoxia imaging in TB patients has been reported. 146 There was 68 Ga-nitroimidazole uptake in TB lesions above background activity with varying levels of radiotracer uptake in different TB lesions. These preliminary works establishing the feasibility of the use of PET probes for the non-invasive imaging of hypoxia in TB hold much potential for future applications in understanding the level of hypoxia in different types of lesions, the temporal changes in lesion hypoxia during the evolution of the disease, and the impact of hypoxia on lesion response to chemotherapy during ATT.…”

Advances in PET and MRI imaging of tumor hypoxia

“…The primary excretion route was the urinary tract, and a lower extent in liver and intestines was observed. In hypoxic regions a low-grade uptake of this tracer was observed (SUV mean of 0.47) but the median lesion-to-muscle ratio was 1.7 ( 129 ).…”