PET imaging of tuberculosis

Tuberculosis (TB) is a significant cause of morbidity and mortality in the world; over 2 billion people are infected with Mycobacterium tuberculosis (Mtb). Most of these people carry the bacteria in quiescent state, resulting in latent TB infection (LTBI). Bacterial infection most commonly resides in the lungs. Lymph nodes are the most common sites of extrapulmonary infection (Peto et al., 2009; Lefebvre et al., 2017), especially in the thoracic region. Bones, central nervous system, and kidneys are also often infected (Gambhir et al., 2017; Ankhar et al., 2018).

The innate immune system responds to encountering Mtb by initiating granuloma formation. Mtb antigens are presented dendritic cells in lymph nodes to lymphocytes, which starts the adaptive immune response ∼4-6 weeks after infection. Immune system tries to contain the bacteria in the granulomas, but Mtb can grow inside granulomas in quiescent state. Granulomas can become fibrotic and obstruct lymphatic vessels. In chronic inflammation, granulomas can develop into organized (tertiary) lymphoid structures, resembling lymph nodes. Transmissive granulomas contain neutrophils, causing necrosis, and spreading of Mtb via lymph and blood.

Diagnosis of TB is challenging: sensitivity of tests is ∼80% and microbiologic cultures take two months to give the result. Immunologic tests can determine exposure to Mtb but not the presence of active TB. Chest X-ray and CT imaging is commonly used for screening, diagnosis, and following treatments response (Skoura et al., 2015). Extrapulmonary TB is diagnosed using CT or MRI. Combined PET/CT and PET/MR can help in the diagnosis of TB. PET imaging in TB is reviewed by Ankhar et al (2018).

[18F]FDG can detect active TB lesions that contain activated leukocytes with high glucose uptake. Tuberculosis is a common reason for false-positive findings in lung cancer imaging with [18F]FDG PET/CT. Dual time-point imaging could help to separate active and inactive pulmonary tuberculomas (Kim et al., 2008). Other PET tracers used for imaging pulmonary TB include 68Ga-citrate, 18F- and 11C-choline, cell proliferation tracer [18F]FLT, angiogenesis tracer [68Ga]alfatide, PSMA tracers, hypoxia tracer [18F]FMISO, [18F]F-, and radiolabelled antibiotics such as isoniazid derivative 2-[18F]INH (Weinstein et al., 2012). Granulomas bear some resemblance with atherosclerotic plaques, and some PET tracers can be useful for detecting both.


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References:

Ankrah AO, Glaudemans AWJM, Maes A, Van de Wiele C, Dierckx RAJO, Vorster M, Sathekge MM. Tuberculosis. Semin Nucl Med. 2018; 48: 108-130. doi: 10.1053/j.semnuclmed.2017.10.005.

Gambhir S, Ravina M, Rangan K, Dixit M, Barai S, Bomanji J; IAEA Extra-pulmonary TB Consortium. Imaging in extrapulmonary tuberculosis. Int J Infect Dis. 2017; 56: 237-247. doi: 10.1016/j.ijid.2016.11.003.

Johnson DH, Via LE, Kim P, Laddy D, Lay C-Y, Weinstein EA, Jain S. Nuclear imaging: a powerful novel approach for tuberculosis. Nucl Med Biol. 2014; 41(10): 777-784. doi: 10.1016/j.nucmedbio.2014.08.005.

Skoura E, Zumla A, Bomanji J. Imaging in tuberculosis. Int J Infect Dis. 2015; 32: 87-93. doi: 10.1016/j.ijid.2014.12.007.



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Updated at: 2019-02-07
Created at: 2019-02-06
Written by: Vesa Oikonen