Comparison of 68Ga-DOTANOC with 18F-FDG using PET/MRI imaging in patients with pulmonary tuberculosis

Abstract

We compared the somatostatin analog radioligand, DOTANOC, with FDG, to determine whether there was increased detection of active or sub-clinical lesions in pulmonary tuberculosis (TB) with DOTANOC. Three groups were recruited: (1) active pulmonary TB; (2) IGRA-positive household TB contacts; (3) pneumonia (non-TB). DOTANOC PET/MRI followed by FDG PET/MRI was performed in active TB and pneumonia groups. TB contacts underwent FDG PET/MRI, then DOTANOC PET/MRI if abnormalities were detected. Quantitative and qualitative analyses were performed for total lung and individual lesions. Eight active TB participants, three TB contacts and three pneumonia patients had paired PET/MRI scans. In the active TB group, median SUVmax [FDG] for parenchymal lesions was 7.69 (range 3.00-15.88); median SUVmax [DOTANOC] was 2.59 (1.48-6.40). Regions of tracer uptake were fairly similar for both radioligands, albeit more diffusely distributed in the FDG scans. In TB contacts, two PET/MRIs had parenchymal lesions detected with FDG (SUVmax 5.50 and 1.82), with corresponding DOTANOC uptake < 1. FDG and DOTANOC uptake was similar in pneumonia patients (SUVmax [FDG] 4.17-6.18; SUVmax [DOTANOC] 2.92-4.78). DOTANOC can detect pulmonary TB lesions, but FDG is more sensitive for both active and sub-clinical lesions. FDG remains the preferred ligand for clinical studies, although DOTANOC may provide additional value for pathogenesis studies. Tuberculosis (TB) disease affects 10 million people worldwide every year, and is the leading cause of death from an infectious disease 1. New TB biomarkers are required for a variety of applications, including detection of subclinical disease for early intervention to prevent disease progression; detection of new active TB cases; and for monitoring of treatment response in clinical practice or in clinical trials of new TB therapies. Positron emission tomography (PET) imaging in combination with structural imaging may have value as a biomarker for detecting subclinical TB disease, active disease where the diagnosis is problematical, and an outcome measure in clinical trials 2-7. The standard PET ligand, [18F]fluoro-2-deoxy-2-d-glucose (FDG), accumulates in cells with high levels of glucose metabolism, and is a non-specific marker of inflammation. There may be additional value in using alternatives to FDG, if these have higher sensitivity or specificity for TB-infected cells 8. Somatostatin analog PET radiotracers are useful in evaluating neuro-endocrine tumours 9-11 and other cancers' cells 12-15 that have upregulated cell surface somatostatin receptors (SSTRs). These receptors are also overexpressed on activated macrophages 16,17 , which are a key cell population infected by TB, residing within granulomas 18,19. Over-expression of somatostatin receptors in granulomas within lymph nodes of TB patients have been visualised using in vitro autoradiography 20 , and SSTR-positive cells have been detected using immunohistochemistry analysis in granulomas from multiple granulomatous conditions 21,22 including pulmon...

Clinical Applications of Somatostatin Receptor (Agonist) PET Tracers beyond Neuroendocrine Tumors

“…SSTR tracer and [ 18 F]FDG PET/MRI imaging were compared in 14 patients with pulmonary tuberculosis by Naftalin et al [ 21 ]. [ 68 Ga]Ga-DOTANOC was able to detect pulmonary lesions, but [ 18 F]FDG was more sensitive for both active and subclinical lesions (see Figure 3 ).…”

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

“…Furthermore, hypoxia PET/CT is known to have inherently low signal-to-noise ratios [56]. One should also consider the different intrinsic physical characteristics between 68 Ga and 18 F, which ultimately affect the spatial resolution and sensitivity of PET/CT images [57,58].…”

CT and 18F-FDG PET abnormalities in contacts with recent tuberculosis infections but negative chest X-ray

“…Of 1638 publications identified in the initial database search, 25 articles studies have applied chest CT, 18 F-FDG PET/CT, or magnetic resonance imaging (MRI) to evaluate asymptomatic close contacts with pulmonary TB patients and normal radiographs (Table 1 ) (Additional file 1 : Fig. 1): 21 CT studies [ 13 – 33 ], two 18 F-FDG PET/CT studies [ 34 , 35 ], and two PET/MR studies [ 36 , 37 ]. Seventeen of the 25 studies were conducted in Asia, followed by Europe.…”