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

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

doi:10.1093/rheumatology/keaa624

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

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

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	2396–2408
Number of pages	14
Journal	Rheumatology
Volume	60
Issue number	5
Early online date	21 Nov 2020
DOIs	https://doi.org/10.1093/rheumatology/keaa624
Publication status	Published - May 2021

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Cite this

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. L., Galette, P., Searle, G. E., Patel, N., Kershaw, L., Gray, C., Ratia, N., van Maurik, A., ... 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

@article{a11c2df4b0084435bf71855b0c16cca0,

title = "Advanced imaging for quantification of abnormalities in the salivary glands of patients with primary Sj{\"o}gren's Syndrome",

abstract = "ObjectivesTo 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.MethodsIn 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.ResultsTwelve 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.ConclusionMolecular imaging and MRI may be useful tools to non-invasively assess loss of glandular function, increased glandular inflammation and fat accumulation in pSS.",

author = "Pilar Jimenez-royo and Michele Bombardieri and Coziana Ciurtin and Michalis Kostapanos and Tappuni, {Anwar R.} and Natasha Jordan and Azeem Saleem and Teresa Fuller and Kathleen Port and Elena Pontarini and Davide Lucchesi and Janiczek, {Robert L.} and Paul Galette and Searle, {Graham E.} and Neel Patel and Lucy Kershaw and Calum Gray and Nirav Ratia and {van Maurik}, Andr{\'e} and {de Groot}, Marius and Nicolas Wisniacki and Mats Bergstrom and Ruth Tarzi",

year = "2021",

month = may,

doi = "10.1093/rheumatology/keaa624",

language = "English",

volume = "60",

pages = "2396–2408",

journal = "Rheumatology",

issn = "1462-0324",

publisher = "Oxford University Press",

number = "5",

}

Jimenez-royo, P, Bombardieri, M, Ciurtin, C, Kostapanos, M, Tappuni, AR, Jordan, N, Saleem, A, Fuller, T, Port, K, Pontarini, E, Lucchesi, D, Janiczek, RL, Galette, P, Searle, GE, Patel, N, Kershaw, L , Gray, C, Ratia, N, van Maurik, A, de Groot, M, Wisniacki, N, Bergstrom, M & Tarzi, R 2021, 'Advanced imaging for quantification of abnormalities in the salivary glands of patients with primary Sjögren's Syndrome', Rheumatology, vol. 60, no. 5, pp. 2396–2408. https://doi.org/10.1093/rheumatology/keaa624

TY - JOUR

T1 - Advanced imaging for quantification of abnormalities in the salivary glands of patients with primary Sjögren's Syndrome

AU - Jimenez-royo, Pilar

AU - Bombardieri, Michele

AU - Ciurtin, Coziana

AU - Kostapanos, Michalis

AU - Tappuni, Anwar R.

AU - Jordan, Natasha

AU - Saleem, Azeem

AU - Fuller, Teresa

AU - Port, Kathleen

AU - Pontarini, Elena

AU - Lucchesi, Davide

AU - Janiczek, Robert L.

AU - Galette, Paul

AU - Searle, Graham E.

AU - Patel, Neel

AU - Kershaw, Lucy

AU - Gray, Calum

AU - Ratia, Nirav

AU - van Maurik, André

AU - de Groot, Marius

AU - Wisniacki, Nicolas

AU - Bergstrom, Mats

AU - Tarzi, Ruth

PY - 2021/5

Y1 - 2021/5

N2 - ObjectivesTo 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.MethodsIn 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.ResultsTwelve 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.ConclusionMolecular imaging and MRI may be useful tools to non-invasively assess loss of glandular function, increased glandular inflammation and fat accumulation in pSS.

AB - ObjectivesTo 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.MethodsIn 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.ResultsTwelve 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.ConclusionMolecular imaging and MRI may be useful tools to non-invasively assess loss of glandular function, increased glandular inflammation and fat accumulation in pSS.

U2 - 10.1093/rheumatology/keaa624

DO - 10.1093/rheumatology/keaa624

M3 - Article

SN - 1462-0324

VL - 60

SP - 2396

EP - 2408

JO - Rheumatology

JF - Rheumatology

IS - 5

ER -

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

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

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