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

Author:

Jimenez-Royo Pilar1,Bombardieri Michele2,Ciurtin Coziana3ORCID,Kostapanos Michalis45,Tappuni Anwar R6,Jordan Natasha7,Saleem Azeem89,Fuller Teresa1,Port Kathleen1,Pontarini Elena2,Lucchesi Davide2,Janiczek Robert1,Galette Paul1,Searle Graham8,Patel Neel1,Kershaw Lucy1011,Gray Calum11,Ratia Nirav1,van Maurik André1,de Groot Marius14,Wisniacki Nicolas1,Bergstrom Mats1,Tarzi Ruth1ORCID

Affiliation:

1. Research and Development, GlaxoSmithKline, Stevenage

2. Experimental Medicine and Rheumatology, Queen Mary University of London, London

3. Centre for Adolescent Rheumatology, University College London, London

4. GlaxoSmithKline Clinical Unit Cambridge, Cambridge

5. Department of Medicine, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge

6. Institute of Dentistry, Queen Mary University of London, London

7. Rheumatology Department, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge

8. Invicro, Centre for Imaging Sciences, A Konica Minolta Company, London

9. Faculty of Health Sciences, University of Hull, Hull

10. Centre for Inflammation Research, University of Edinburgh

11. Edinburgh Imaging, University of Edinburgh, Edinburgh

Abstract

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.

Funder

GlaxoSmithKline

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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