PET/CT imaging of Mycobacterium tuberculosis infection

Abstract

Tuberculosis has a high morbidity and mortality worldwide. Mycobacterium tuberculosis (Mtb) has a complex pathophysiology; it is an aerobic bacillus capable of surviving in anaerobic conditions in a latent state for a very long time before reactivation to active disease. In the latent tuberculosis infection, the individual has no clinical evidence of active disease, but exhibits a hypersensitive response to proteins of Mtb. Only some 5-10 % of latently infected individuals appear to have reactivation of tuberculosis at any one time point after infection, and neither imaging nor immune tests have been shown to predict tuberculosis reactivation reliably. The complex pathology of the organism provides multiple molecular targets for imaging the infection and targeting therapy. Positron emission tomography (PET) integrated with computer tomography (CT) provides a unique opportunity to noninvasively image the whole body for diagnosing, staging and assessing therapy response in many infectious and inflammatory diseases. PET/CT is a powerful noninvasive tool that can rapidly provide three-dimensional views of disease deep within the body and conduct longitudinal assessment over time in one particular patient. Some PET tracers, such as ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), have been found to be useful in various infectious diseases for detection, assessing disease activity, staging and monitoring response to therapy. This tracer has also been used for imaging tuberculosis. ¹⁸F-FDG PET relies on the glucose uptake of inflammatory cells as a result of the respiratory burst that occurs with infection. Other PET tracers have also been used to image different aspects of the pathology or microbiology of Mtb. The synthesis of the complex cell membrane of the bacilli for example can be imaged with ¹¹C-choline or ¹⁸F-fluoroethylcholine PET/CT while the uptake of amino acids during cell growth can be imaged by 3'-deoxy-3'-[¹⁸F]fluoro-l-thymidine. PET/CT provides a noninvasive and sensitive method of assessing histopathological information on different aspects of tuberculosis and is already playing a role in the management of tuberculosis. As our understanding of the pathophysiology of tuberculosis increases, the role of PET/CT in the management of this disease would become more important. In this review, we highlight the various tracers that have been used in tuberculosis and explain the underlying mechanisms for their use.

Keywords: 18F-fluoroethylcholine; 3′-Deoxy-3′-[18F]fluoro-l-thymidine; 68Ga-citrate; PET/CT; Tuberculosis.

Fig. 1

¹⁸F-FDG PET/CT scan before anti-TB treatment and 2 months after initiation of treatment for interim assessment of treatment response. a Maximum intensity projection (MIP) image before treatment (PET images only), showing extensive disease: pulmonary, cervical, axillary, mediastinal, abdominal, pelvic and inguinal lymph nodes, hepatic and skeletal metastasis to the lumbar spine and right humerus. b MIP image after 2 months of anti-TB treatment (PET images only): complete metabolic response of the pulmonary and right humeral lesions and the pelvic and inguinal lymph nodes. Good metabolic response in the mediastinal, cervical and axillary nodes. Active disease is still present in the lumber spine with progression of the hepatic lesions. c Transverse scans showing axillary nodes before treatment (PET and integrated PET/CT images). d Transverse scans showing response of axillary nodes after 2 month of anti-TB therapy; nodal uptake diminished but still present