may help explain biology of such lesion and help in the development of therapeutic intervention in these lesions. 18F‐FDG‐PET/CT may also be useful to identify old healed cavities that are more likely to relapse. An 89Zr labelled PET tracer has been found useful in detection of CD4 and CD8 cells T lymphocytes.141 This tracer may have a potential role in the assessment of TB lesions that are at risk of cavitation before it occurs and may help develop strategies to prevent irreversible damage.
LTBI
18F‐FDG‐PET/CT has been reported to assess the risk of development of active TB by assessing lung inflammation in humans.12 Fully quantitative methods for assessing total lung inflammation with 18F‐
FDG‐PET/CT which correct for air and lung have been described in the literature.142 Modified versions of these methods that would be practical in the clinical setting will be useful in assessing the risk for LTBI patients to progress. The core of most mature TB granulomas is necrotic and hypoxic.143 In LTBI hypoxia was determined to be one of the factors that switched metabolism of Mtb to the quiescent state. Imaging with hypoxic tracers may be beneficial to assess the extent of disease LTBI and help understand the pathology.76 One study evaluated whether PET was able to evaluate the early events in LTBI in humans using 18F‐FDG. Five people were recruited in the study. The participants were asymptomatic, had normal chest radiographs and positive QuantiFERON gold assays. Four of the participants had positive PET scans involving mediastinal lymph nodes. None of the participants had
18F‐FDG uptake in the lungs. The patient who had no FDG uptake had a calcified lung granuloma and calcified hilar nodes noted on CT. None of the 18F‐FDG avid nodes met the radiological criteria for an enlarged lymph node.35 This study suggests that 18F‐FDG‐PET/CT may be useful to study early events and probably the course of LTBI.
TB and fever of unknown origin
18F‐FDG‐PET/CT has been found to be useful in the evaluation of patients with FUO and TB is frequently a cause of the fever with or without HIV.116, 144, 145 More than 50% of patients with FUO were eventually diagnosed with TB by 18F‐FDG‐PET/CT in one series.144
TB and children
The use of 18F‐FDG PET/CT in TB in children does not differ from that in adults.146 The tissues of children are more radiosensitive and modalities not using ionising radiation would be preferred when imaging them. The use of PET/MRI may reduce radiation burden and offer advantages of 18F‐FDG‐PET in tuberculosis imaging for specific sites such as TB spondylitis.147
Other preclinical PET/CT imaging in TB
In the preclinical setting, F18 sodium fluoride has been used in the detection of microcalcification that may occur in pulmonary TB lesions. A number of drug labelled PET tracers have been evaluated in non‐
human primates such as C11 labeled rifampicin, isoniazid and ethambutol. These studies were used to evaluate biodistribution of these drugs in the body.4 The biodistribution of F18 labelled pyrazinamide analogue in a mouse model has also been studied.148
Conclusion and future perspectives
PET/CT with 18F‐FDG is useful in the management of patients with TB. In evaluation of patients with
18F‐FDG‐PET/CT, there has been an evolution from TB merely being a nuisance, causing false positive
184 185
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studies in oncology patients, to a place where PET/CT is useful for evaluation of different aspects of the infection. 18F‐FDG‐PET/CT helps with the diagnosis of TB in patients with FUO and helps confirm the diagnosis of TB early by revealing site of biopsy in patients with suspected TB. The pre‐therapeutic scan gives a metabolic map staging the disease and revealing previously undiagnosed sites. 18F‐FDG‐
PET/CT has been used to identify patients with subclinical TB. The use of lung inflammation as determined by 18F‐FDG‐PET/CT is increasingly finding a role in stratifying patients likely to develop TB.
Available PET tracers are helping us understand the pathogenesis of the disease.76 The ability of PET/CT to image ligands or receptors on immune cells allowing predominant cell types in TB lesions to be imaged could potentially not only increase our understanding of the spectrum of lesions found in both LTBI and active TB but allow personalized therapeutic intervention strategies based on the PET findings. A radiopharmaceutical which will be able to identify TB, distinguishing it from other pathology would make an impact in clinical practice and several compounds are being evaluated. One such candidate is the modified trehalose analogue. Trehalose is a non‐mammalian disaccharide important for mycobacterial cell wall synthesis and virulence. Trehalose analogues have recently been explored with detectable tags in detection of mycobacteria with some promising results.149
In order to achieve the goals of the ‘End TB strategy’ of the WHO, intensified research and innovation has been identified as one of the pillars and components.150 PET/CT imaging of TB is well positioned to have a major impact especially in the areas of research and in vitro assessment of new intervention strategies against the infection. The role of PET/CT imaging in TB is likely to evolve as new data about the role of PET/CT management in TB becomes available. Development of new tracers or repurposed old tracers may also play a significant role in management of TB in the near future.
Acknowledgement: Department of Nuclear Medicine, University of Pretoria and Steve Biko Academic Hospital
Conflict of interest‐ none
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