Skip to main content
Top
Published in: EJNMMI Research 1/2016

Open Access 01-12-2016 | Original research

Somatostatin receptor scintigraphy in patients with rheumatoid arthritis and secondary Sjögren’s syndrome treated with Infliximab: a pilot study

Authors: L. K. Anzola-Fuentes, M. Chianelli, F. Galli, A. W. J. M. Glaudemans, L. Martin Martin, V. Todino, A. Migliore, A. Signore

Published in: EJNMMI Research | Issue 1/2016

Login to get access

Abstract

Background

Human T lymphocytes infiltrating tissues in autoimmune diseases are known to express somatostatin receptors amongst other activation markers. In this study, we evaluated whether somatostatin receptor scintigraphy (SRS) using a radiolabelled somatostatin analogue (99mTc-EDDA/tricine-HYNIC-tyr(3)-octreotide (99mTc-EDDA/HYNIC-TOC)) is able to detect the presence of immune-mediated processes in patients with rheumatoid arthritis and secondary Sjögren’s syndrome. We also aimed to evaluate whether positivity to SRS was predictive of therapeutic response and if SRS could be used for monitoring the efficacy of immunomodulatory treatment.

Methods

Eighteen patients with rheumatoid arthritis and secondary Sjögren’s syndrome not responding to conventional treatment were recruited for treatment with infliximab, a monoclonal antibody against TNF-α. All patients had complete blood cell count, renal and liver function tests, measurements of ESR, CRP, ANA, ENA, and anti-dsDNA antibodies, functional salivary gland scintigraphy, labial biopsy, and ophthalmologic assessment with Schirmer’s test and tear film break-up time (BUT). Diagnosis was made according to the revised criteria of the American-European Consensus Group. All patients underwent SRS at baseline and after 3–6 months of therapy with infliximab. Eleven out of 18 had repeat SRS images. Images of the salivary glands and major joints were acquired 3 h after injection of 370 MBq of 99mTc-EDDA/HYNIC-TOC. Image analysis was performed semi-quantitatively.

Results

All patients showed uptake of 99mTc-EDDA/HYNIC-TOC in the joints. Salivary glands also showed variable radiopharmaceutical uptake in 12 out of 18 patients, but all patients showed presence of lymphocytic infiltration at labial salivary gland biopsy. All patients, who repeated the study after treatment, showed significant reduction of somatostatin uptake in the joints but not in the salivary glands.

Conclusions

SRS using 99mTc-EDDA/HYNIC-TOC may be a useful imaging tool to assess disease activity and extent in patients with rheumatoid arthritis and may help to detect secondary Sjögren’s syndrome. It may also aid therapy decision-making with anti-TNFα antibodies in the joints but not in salivary glands.
Literature
1.
go back to reference Ramos-Casals M, Brito-Zeron P, Font J. The overlap of Sjogren’s syndrome with other systemic autoimmune diseases. Arthritis Rheum. 2007;36:246–55.CrossRef Ramos-Casals M, Brito-Zeron P, Font J. The overlap of Sjogren’s syndrome with other systemic autoimmune diseases. Arthritis Rheum. 2007;36:246–55.CrossRef
2.
go back to reference Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjögren syndrome. Arch Intern Med. 2004;164:1275–84.CrossRefPubMed Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjögren syndrome. Arch Intern Med. 2004;164:1275–84.CrossRefPubMed
3.
go back to reference Daridon C, Guerrier T, Devauchelle V, Saraux A, Pers JO, Youinou P. Polarization of B effector cells in Sjögren’s syndrome. Autoimmun Rev. 2007;6:427–31.CrossRefPubMed Daridon C, Guerrier T, Devauchelle V, Saraux A, Pers JO, Youinou P. Polarization of B effector cells in Sjögren’s syndrome. Autoimmun Rev. 2007;6:427–31.CrossRefPubMed
4.
go back to reference Choy EHS, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001;344:907–16.CrossRefPubMed Choy EHS, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001;344:907–16.CrossRefPubMed
5.
go back to reference Lapadula G, Marchesoni A, Armuzzi A, Blandizzi C, Caporali R, Chimenti S, et al. Adalimumab in the treatment of immune-mediated diseases. Int J Immunopathol Pharmacol. 2014;27:33–48. Lapadula G, Marchesoni A, Armuzzi A, Blandizzi C, Caporali R, Chimenti S, et al. Adalimumab in the treatment of immune-mediated diseases. Int J Immunopathol Pharmacol. 2014;27:33–48.
6.
go back to reference Sankar V, Brennan MT, Kok MR, Leakan RA, Smith JA, Manny J, et al. Etanercept in Sjogren’s syndrome: a twelve-week ramdomized, double-blind, placebo-controlled pilot clinical trial. Arthritis Rheum. 2004;50:2240–5. Sankar V, Brennan MT, Kok MR, Leakan RA, Smith JA, Manny J, et al. Etanercept in Sjogren’s syndrome: a twelve-week ramdomized, double-blind, placebo-controlled pilot clinical trial. Arthritis Rheum. 2004;50:2240–5.
7.
go back to reference Taylor PC, Williams RO, Feldmann M. Tumour necrosis factor-α as a therapeutic target for immune-mediated inflammatory diseases. Curr Opin Biotech. 2004;15:557–63.CrossRefPubMed Taylor PC, Williams RO, Feldmann M. Tumour necrosis factor-α as a therapeutic target for immune-mediated inflammatory diseases. Curr Opin Biotech. 2004;15:557–63.CrossRefPubMed
8.
go back to reference Glaudemans AW, Dierckx RA, Kallenberg CG, Fuentes KL. The role of radiolabelled anti-TNFα monoclonal antibodies for diagnostic purposes and therapy evaluation. Q J Nucl Med Mol Imaging. 2010;54:639–55.PubMed Glaudemans AW, Dierckx RA, Kallenberg CG, Fuentes KL. The role of radiolabelled anti-TNFα monoclonal antibodies for diagnostic purposes and therapy evaluation. Q J Nucl Med Mol Imaging. 2010;54:639–55.PubMed
9.
go back to reference Duet M, Liot F. Somatostatin and somatostatin analog scintigraphy: any benefits for rheumatologic patients. Joint Bone Spine. 2004;71:530–5.CrossRefPubMed Duet M, Liot F. Somatostatin and somatostatin analog scintigraphy: any benefits for rheumatologic patients. Joint Bone Spine. 2004;71:530–5.CrossRefPubMed
10.
go back to reference Van Hagen M, Krenning EP, Kwekkeboom DJ, Reubi JC, Anker-Lugtenburg PJ, Löwenberg B, et al. Somatostatin and the immune and haematopoetic system: a review. Eur J Clin Invest. 1994;24:91–9. Van Hagen M, Krenning EP, Kwekkeboom DJ, Reubi JC, Anker-Lugtenburg PJ, Löwenberg B, et al. Somatostatin and the immune and haematopoetic system: a review. Eur J Clin Invest. 1994;24:91–9.
11.
go back to reference Lichtenauer-Kaligis EG, Dalm VA, Oomen SP, Mooij DM, van Hagen PM, Lamberts SW, et al. Differential expression of somatostatin receptor subtypes in human peripheral blood mononuclear cell subsets. Eur J Endocrinol. 2004;150:565–77. Lichtenauer-Kaligis EG, Dalm VA, Oomen SP, Mooij DM, van Hagen PM, Lamberts SW, et al. Differential expression of somatostatin receptor subtypes in human peripheral blood mononuclear cell subsets. Eur J Endocrinol. 2004;150:565–77.
12.
go back to reference Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Di. 2002;61:554–8. Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Di. 2002;61:554–8.
13.
go back to reference Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Eng J Med. 2000;343:1594–602. Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Eng J Med. 2000;343:1594–602.
14.
go back to reference Decristoforo C, Mendelez-Alafort L, Sosabowski JK, Mather SJ. 99mTc-HYNIC-[Tyr3]-octreotide for imaging of somatostatin-receptor-positive tumors: preclinical evaluation and comparison with 111In-octreotide. J Nucl Med. 2000;41:1114.PubMed Decristoforo C, Mendelez-Alafort L, Sosabowski JK, Mather SJ. 99mTc-HYNIC-[Tyr3]-octreotide for imaging of somatostatin-receptor-positive tumors: preclinical evaluation and comparison with 111In-octreotide. J Nucl Med. 2000;41:1114.PubMed
15.
go back to reference Mjaavatten MD, Bykerk VP. Early rheumatoid arthritis: the performance of the 2010 ACR/EULAR criteria for diagnosing RA. Best Pract Res Clin Rheumatol. 2013;27:451–66.CrossRefPubMed Mjaavatten MD, Bykerk VP. Early rheumatoid arthritis: the performance of the 2010 ACR/EULAR criteria for diagnosing RA. Best Pract Res Clin Rheumatol. 2013;27:451–66.CrossRefPubMed
16.
go back to reference Reubi JC, Waser B, Markusse HM, Krenning EP, VanHagen M, Laissue JA. Vascular somatostatin receptors in synovium from patients with rheumatoid arthritis. Eur J Pharmacol. 1994;271:371–8.CrossRefPubMed Reubi JC, Waser B, Markusse HM, Krenning EP, VanHagen M, Laissue JA. Vascular somatostatin receptors in synovium from patients with rheumatoid arthritis. Eur J Pharmacol. 1994;271:371–8.CrossRefPubMed
17.
go back to reference Chowers Y, Cahalon L, Lahav M, Schor H, Tal R, Bar-Meir S, et al. Somatostatin through its specific receptors inhibits spontaneous and TNF-α and bacteria-induced IL-8 and IL-1B secretion from instestinal epithelial cells. J Immunol. 2000;165:2955–61. Chowers Y, Cahalon L, Lahav M, Schor H, Tal R, Bar-Meir S, et al. Somatostatin through its specific receptors inhibits spontaneous and TNF-α and bacteria-induced IL-8 and IL-1B secretion from instestinal epithelial cells. J Immunol. 2000;165:2955–61.
18.
go back to reference Takeba Y, Suzuki N, Takeno M, Asai T, Tsuboi S, Hoshino T, et al. Modulation of synovial cell function by somatostatin in patients with rheumatoid arthritis. Arthritis Rheum. 1997;40(12):2128–38. Takeba Y, Suzuki N, Takeno M, Asai T, Tsuboi S, Hoshino T, et al. Modulation of synovial cell function by somatostatin in patients with rheumatoid arthritis. Arthritis Rheum. 1997;40(12):2128–38.
19.
go back to reference Vanhagen PM, Markusse HM, Lamberts SW, Kwekkeboom DJ, Reubi JC, Krenning EP. Somatostatin receptor imaging. The presence of somatostatin receptors in rheumatoid arthritis. Arthritis Rheum. 1994;37:1521–7.CrossRefPubMed Vanhagen PM, Markusse HM, Lamberts SW, Kwekkeboom DJ, Reubi JC, Krenning EP. Somatostatin receptor imaging. The presence of somatostatin receptors in rheumatoid arthritis. Arthritis Rheum. 1994;37:1521–7.CrossRefPubMed
20.
go back to reference Adams RL, Adams IP, Lindow SW, Zhong W, Atkia SL. Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endhotelium. Br J Cancer. 2005;25:1493–8.CrossRef Adams RL, Adams IP, Lindow SW, Zhong W, Atkia SL. Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endhotelium. Br J Cancer. 2005;25:1493–8.CrossRef
21.
go back to reference Cascini GL, Curcurullo V, Mansi L. The non tumour uptake of 111In-octreotide creates new clinical indications in benign diseases, but also in oncology. Q J Nucl Med Mol Imaging. 2010;54:24–36.PubMed Cascini GL, Curcurullo V, Mansi L. The non tumour uptake of 111In-octreotide creates new clinical indications in benign diseases, but also in oncology. Q J Nucl Med Mol Imaging. 2010;54:24–36.PubMed
22.
go back to reference Paran D, Elkayam O, Mayo A, Paran H, Amit M, Yaron M, et al. A pilot study of a long acting somatostatin analogue for the treatment of refractory rheumatoid arthritis. Ann Rheum Dis. 2001;60:888–91. Paran D, Elkayam O, Mayo A, Paran H, Amit M, Yaron M, et al. A pilot study of a long acting somatostatin analogue for the treatment of refractory rheumatoid arthritis. Ann Rheum Dis. 2001;60:888–91.
23.
go back to reference Jara LJ, Navarro C, Brito-Zeron Mdel P, Garcia-Carrasco M, Escarcega RO, Ramos-Casals M. Thyroid disease in Sjogren’s syndrome. Clin Rheumatol. 2007;26:1601–6.CrossRefPubMed Jara LJ, Navarro C, Brito-Zeron Mdel P, Garcia-Carrasco M, Escarcega RO, Ramos-Casals M. Thyroid disease in Sjogren’s syndrome. Clin Rheumatol. 2007;26:1601–6.CrossRefPubMed
24.
go back to reference Mariette X, Ravaud P, Steinfeld S, Baron G, Goetz J, Hachulla E, et al. Inefficacy of infliximab in primary Sjögren’s syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjögren’s Syndrome (TRIPSS). Arthritis Rheum. 2004;50:1270–6. Mariette X, Ravaud P, Steinfeld S, Baron G, Goetz J, Hachulla E, et al. Inefficacy of infliximab in primary Sjögren’s syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjögren’s Syndrome (TRIPSS). Arthritis Rheum. 2004;50:1270–6.
25.
go back to reference Soto-Rojas AE, Kraus A. The oral side of Sjögren’s syndrome. Diagnosis and treatment. A review. Arch Med Res. 2002;33:95–106.CrossRefPubMed Soto-Rojas AE, Kraus A. The oral side of Sjögren’s syndrome. Diagnosis and treatment. A review. Arch Med Res. 2002;33:95–106.CrossRefPubMed
26.
go back to reference Leroy JP, Pennec YL, Soulier C, Berthelot JM, Letoux G, Youinou P. Follow up study of labial salivary gland lesions in primary Sjogren’s syndrome. Ann Rheum Dis. 1992;51:777–80.CrossRefPubMedPubMedCentral Leroy JP, Pennec YL, Soulier C, Berthelot JM, Letoux G, Youinou P. Follow up study of labial salivary gland lesions in primary Sjogren’s syndrome. Ann Rheum Dis. 1992;51:777–80.CrossRefPubMedPubMedCentral
27.
go back to reference Vitali C, Moutsopoulus HM, Bomabardieri S. The European community study group on diagnostic criteria for Sjrogen’s syndrome. Sensitivity and specificity of tests for ocular and oral involment in Sjrögen’s syndrome. Ann Rheum Dis. 1994;53:637–47.CrossRefPubMedPubMedCentral Vitali C, Moutsopoulus HM, Bomabardieri S. The European community study group on diagnostic criteria for Sjrogen’s syndrome. Sensitivity and specificity of tests for ocular and oral involment in Sjrögen’s syndrome. Ann Rheum Dis. 1994;53:637–47.CrossRefPubMedPubMedCentral
Metadata
Title
Somatostatin receptor scintigraphy in patients with rheumatoid arthritis and secondary Sjögren’s syndrome treated with Infliximab: a pilot study
Authors
L. K. Anzola-Fuentes
M. Chianelli
F. Galli
A. W. J. M. Glaudemans
L. Martin Martin
V. Todino
A. Migliore
A. Signore
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2016
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-016-0202-y

Other articles of this Issue 1/2016

EJNMMI Research 1/2016 Go to the issue