Advanced imaging for quantification of abnormalities in the salivary glands of patients with primary Sjögren's syndrome

Jimenez-Royo, Pilar; Bombardieri, Michele; Ciurtin, Coziana; Kostapanos, Michalis; Tappuni, Anwar R; Jordan, Natasha; Saleem, Azeem; Fuller, Teresa; Port, Kathleen; Pontarini, Elena; Lucchesi, Davide; Janiczek, Robert; Galette, Paul; Searle, Graham; Patel, Neel; Kershaw, Lucy; Gray, Calum; Ratia, Nirav; van Maurik, André; de Groot, Marius; Wisniacki, Nicolas; Bergstrom, Mats; Tarzi, Ruth

Abstract

OBJECTIVES: To assess non-invasive imaging for detection and quantification of gland structure, inflammation and function in patients with primary Sjogren's syndrome (pSS) using PET-CT with 11C-Methionine (11C-MET; radiolabelled amino acid), and 18F-fluorodeoxyglucose (18F-FDG; glucose uptake marker), to assess protein synthesis and inflammation, respectively; multiparametric MRI evaluated salivary gland structural and physiological changes. METHODS: In this imaging/clinical/histology comparative study (GSK study 203818; NCT02899377) patients with pSS and age- and sex-matched healthy volunteers underwent MRI of the salivary glands and 11C-MET PET-CT. Patients also underwent 18F-FDG PET-CT and labial salivary gland biopsies. Clinical and biomarker assessments were performed. Primary endpoints were semi-quantitative parameters of 11C-MET and 18F-FDG uptake in submandibular and parotid salivary glands and quantitative MRI measures of structure and inflammation. Clinical and minor salivary gland histological parameter correlations were explored. RESULTS: Twelve patients with pSS and 13 healthy volunteers were included. Lower 11C-MET uptake in parotid, submandibular and lacrimal glands, lower submandibular gland volume, higher MRI fat fraction, and lower pure diffusion in parotid and submandibular glands were observed in patients vs healthy volunteer, consistent with reduced synthetic function. Disease duration correlated positively with fat fraction and negatively with 11C-MET and 18F-FDG uptake, consistent with impaired function, inflammation and fatty replacement over time. Lacrimal gland 11C-MET uptake positively correlated with tear flow in patients, and parotid gland 18F-FDG uptake positively correlated with salivary gland CD20+ B-cell infiltration. CONCLUSION: Molecular imaging and MRI may be useful tools to non-invasively assess loss of glandular function, increased glandular inflammation and fat accumulation in pSS.

Citation

Jimenez-Royo, P., Bombardieri, M., Ciurtin, C., Kostapanos, M., Tappuni, A. R., Jordan, N., Saleem, A., Fuller, T., Port, K., Pontarini, E., Lucchesi, D., Janiczek, R., Galette, P., Searle, G., Patel, N., Kershaw, L., Gray, C., Ratia, N., van Maurik, A., de Groot, M., …Tarzi, R. (2021). Advanced imaging for quantification of abnormalities in the salivary glands of patients with primary Sjögren's syndrome. Rheumatology, 60(5), 2396-2408. https://doi.org/10.1093/rheumatology/keaa624

• Journal Article Type: Article
• Acceptance Date: Aug 21, 2020
• Online Publication Date: Nov 21, 2020
• Publication Date: May 14, 2021
• Deposit Date: Feb 10, 2021
• Publicly Available Date: Feb 11, 2021
• Journal: Rheumatology (Oxford, England)
• Print ISSN: 1462-0324
• Electronic ISSN: 1462-0332
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 60
• Issue: 5
• Article Number: keaa624
• Pages: 2396-2408
• DOI: https://doi.org/10.1093/rheumatology/keaa624
• Keywords: SS; MRI; CT scanning; Radionuclide imaging; Diagnostic imaging; Outcome measures and histopathology
• Public URL: https://hull-repository.worktribe.com/output/3692997