Evaluation of 11C-acetate PET Imaging as a Novel Approach to Detecting Pathology in Pulmonary TB

Imaging using 11C-acetate PET (positron emission tomography) in patients with tuberculosis (TB) may be able to detect non-replicating persister bacilli. This may permit identification of those patients at risk of relapse following completion of TB treatment. The main aim of this pilot study is to assess the ability of 11C-acetate PET to detect pulmonary lesions in individuals with active pulmonary TB.

Novel biomarkers for detecting pulmonary TB and response to treatment are sorely needed. PET in conjunction with either CT (computed tomography) or MRI (magnetic resonance imaging) scanning allows assessment of the metabolic activity of lesions as well as the structural anatomy of the lung. The standard radiolabelled tracer for PET is 18F-fluorodeoxyglucose (FDG) which labels metabolically active cells. However, one of the main limitations of FDG is the non-specific uptake leading to difficulty differentiating between tumours, infection and inflammatory pathologies. 11C-acetate is a PET ligand used currently to image various conditions but has not been used to identify TB lesions previously. 11C-acetate may be taken up by the lipid bodies in the dormant bacteria in TB, enabling visualization of this sub-population of bacteria. Using the 11C-acetate ligand for imaging pulmonary TB may add to the utility of PET scanning, potentially allowing monitoring of drug activity against the persister population and identification of those patients who may be at risk of relapse following drug therapy. This pilot study will compare 11C-acetate to the standard ligand, FDG, using PET/CT and PET/MRI. The target population for this study is those individuals with confirmed pulmonary TB who have a high chance of demonstrable bacillary burden who are therefore likely to have populations of persister bacteria in the lungs.

Inclusion Criteria: Age 21 years and above Willing to comply with the study visits and procedures Willing and able to provide written informed consent Clinical diagnosis of pulmonary TB with characteristic symptoms and compatible X-ray findings plus microbiological confirmation with one or more of (i) Acid-fast bacilli (AFB) smear-positive or (ii) molecular test positive or (iii) TB culture positive. Tests done at any time during the current episode of TB are acceptable for diagnostic purposes Not on TB treatment or have completed less than 8 weeks of TB treatment Exclusion Criteria: Diabetes that is, in the judgment of the investigator, so poorly controlled that it would prevent adequate PET scanning Cardiac pacemaker, aneurysm clip or other metallic implant considered unsafe for MRI Known chronic kidney disease Occupation involving substantial exposure to radiation History of medical procedures in the last year involving substantial exposure to radiation (>2mSv) Malignancy requiring chemotherapy or radiation Women who are currently pregnant or breastfeeding