Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-07-2009 | Original Article

¹⁸F-FDG PET, genotype-corrected ACE and sIL-2R in newly diagnosed sarcoidosis

Authors: Ruth G. Keijsers, Fred J. Verzijlbergen, Wim J. Oyen, Jules M. van den Bosch, Henk J. Ruven, Heleen van Velzen-Blad, Jan C. Grutters

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 7/2009

Abstract

Purpose

Angiotensin-converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R) are serological markers, widely used for determining sarcoidosis activity. ¹⁸F-FDG PET has proven to be a sensitive technique in the imaging of sarcoidosis. The aim of this study was to determine sensitivity of ¹⁸F-FDG PET, genotype-corrected ACE and sIL-2R in active sarcoidosis as well as their correlation.

Methods

This retrospective study included 36 newly diagnosed, symptomatic sarcoidosis patients. ACE and sIL-2R levels were simultaneously obtained within 4 weeks of ¹⁸F-FDG PET. ACE was corrected for genotype and expressed as Z-score. ¹⁸F-FDG PET was visually evaluated and scored as positive or negative. Maximum and average standardized uptake values (SUV_max and SUV_avg) were compared with ACE and sIL-2R.

Results

¹⁸F-FDG PET was found positive in 34 of 36 patients (94%). Thirteen patients (36%) showed an increased ACE with the highest sensitivity found in patients with the I/I genotype (67%). Seventeen patients (47%) showed an increased sIL-2R. No correlation was found between SUV and ACE or sIL-2R. Increased ACE and sIL-2R correlated with a positive ¹⁸F-FDG PET in 12 patients (92%) and 16 patients (94%), respectively.

Conclusion

¹⁸F-FDG PET is a very sensitive technique to assess active sarcoidosis, in contrast with ACE and sIL-2R, suggesting a pivotal role for ¹⁸F-FDG PET in future sarcoidosis assessment.

Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med 2007;357:2153–65. doi:10.1056/NEJMra071714.PubMedCrossRef

Baughman RP, Lower EE, du Bois RM. Sarcoidosis. Lancet 2003;361:1111–8. doi:10.1016/S0140–6736(03)12888–7.PubMedCrossRef

Gilbert S, Steinbrech DS, Landas SK, Hunninghake GW. Amounts of angiotensin-converting enzyme mRNA reflect the burden of granulomas in granulomatous lung disease. Am Rev Respir Dis 1993;148:483–6.PubMed

Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, et al. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol 1985;135:3172–7.PubMed

Silverstein E, Friedland J, Lyons HA, Gourin A. Elevation of angiotensin-converting enzyme in granulomatous lymph nodes and serum in sarcoidosis: clinical and possible pathogenic significance. Ann N Y Acad Sci 1976;278:498–513. doi:10.1111/j.1749–6632.1976.tb47062.x.PubMedCrossRef

Studdy PR, Lapworth R, Bird R. Angiotensin-converting enzyme and its clinical significance–a review. J Clin Pathol 1983;36:938–47. doi:10.1136/jcp.36.8.938.PubMedCrossRef

Bunting PS, Szalai JP, Katic M. Diagnostic aspects of angiotensin converting enzyme in pulmonary sarcoidosis. Clin Biochem 1987;20:213–9. doi:10.1016/S0009–9120(87)80123–6.PubMedCrossRef

Klech H, Kohn H, Kummer F, Mostbeck A. Assessment of activity in sarcoidosis. Sensitivity and specificity of 67gallium scintigraphy, serum ACE levels, chest roentgenography, and blood lymphocyte subpopulations. Chest 1982;82:732–8. doi:10.1378/chest.82.6.732.PubMedCrossRef

Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343–6. doi:10.1172/JCI114844.PubMedCrossRef

10.

Arbustini E, Grasso M, Leo G, Tinelli C, Fasani R, Diegoli M, et al. Polymorphism of angiotensin-converting enzyme gene in sarcoidosis. Am J Respir Crit Care Med 1996;153:851–4.PubMed

11.

Sharma P, Smith I, Maguire G, Stewart S, Shneerson J, Brown MJ. Clinical value of ACE genotyping in diagnosis of sarcoidosis. Lancet 1997;349:1602–3. doi:10.1016/S0140–6736(05)61631–5.PubMedCrossRef

12.

Stokes GS, Monaghan JC, Schrader AP, Glenn CL, Ryan M, Morris BJ. Influence of angiotensin converting enzyme (ACE) genotype on interpretation of diagnostic tests for serum ACE activity. Aust N Z J Med 1999;29:315–8.PubMed

13.

Tomita H, Ina Y, Sugiura Y, Sato S, Kawaguchi H, Morishita M, et al. Polymorphism in the angiotensin-converting enzyme (ACE) gene and sarcoidosis. Am J Respir Crit Care Med 1997;156:255–9.PubMed

14.

Müller-Quernheim J. Serum markers for the staging of disease activity of sarcoidosis and other interstitial lung diseases of unknown etiology. Sarcoidosis Vasc Diffuse Lung Dis 1998;15:22–37.PubMed

15.

Rothkrantz-Kos S, van Dieijen-Visser MP, Mulder PG, Drent M. Potential usefulness of inflammatory markers to monitor respiratory functional impairment in sarcoidosis. Clin Chem 2003;49:1510–7. doi:10.1373/49.9.1510.PubMedCrossRef

16.

Grutters JC, Fellrath JM, Mulder L, Janssen R, van den Bosch JM, van Velzen-Blad H. Serum soluble interleukin-2 receptor measurement in patients with sarcoidosis: a clinical evaluation. Chest 2003;124:186–95. doi:10.1378/chest.124.1.186.PubMedCrossRef

17.

Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med 1999;160:736–55.

18.

Boellaard R, Oyen WJ, Hoekstra CJ, Hoekstra OS, Visser EP, Willemsen AT, et al. The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-centre trials. Eur J Nucl Med Mol Imaging 2008;35:2320–33. doi:10.1007/s00259–008–0874–2.PubMedCrossRef

19.

Hurst PL, Lovell-Smith CJ. Optimized assay for serum angiotensin-converting enzyme activity. Clin Chem 1981;27:2048–52.PubMed

20.

Neels HM, Scharpé SL, van Sande ME, Verkerk RM, Van Acker KJ. Improved micromethod for assay of serum angiotensin converting enzyme. Clin Chem 1982;28:1352–5.PubMed

21.

Kruit A, Grutters JC, Gerritsen WB, Kos S, Wodzig WK, van den Bosch JM, et al. ACE I/D-corrected Z-scores to identify normal and elevated ACE activity in sarcoidosis. Respir Med 2007;101:510–5. doi:10.1016/j.rmed.2006.06.025.PubMedCrossRef

22.

Crabtree JE, Juby LD, Heatley RV, Lobo AJ, Bullimore DW, Axon AT. Soluble interleukin-2 receptor in Crohn’s disease: relation of serum concentrations to disease activity. Gut 1990;31:1033–6. doi:10.1136/gut.31.9.1033.PubMedCrossRef

23.

Zerler B. The soluble interleukin-2 receptor as a marker for human neoplasia and immune status. Cancer Cells 1991;3:471–9.PubMed

24.

Braun JJ, Kessler R, Constantinesco A, Imperiale A. (18)F-FDG PET/CT in sarcoidosis management: review and report of 20 cases. Eur J Nucl Med Mol Imaging 2008;35:1537–43. doi:10.1007/s00259–008–0770–9.PubMedCrossRef

25.

Yamada Y, Uchida Y, Tatsumi K, Yamaguchi T, Kimura H, Kitahara H, et al. Fluorine-18-fluorodeoxyglucose and carbon-11-methionine evaluation of lymphadenopathy in sarcoidosis. J Nucl Med 1998;39:1160–6.PubMed

26.

Nishiyama Y, Yamamoto Y, Fukunaga K, Takinami H, Iwado Y, Satoh K, et al. Comparative evaluation of 18F-FDG PET and 67Ga scintigraphy in patients with sarcoidosis. J Nucl Med 2006;47:1571–6.PubMed

27.

Bons JA, Drent M, Bouwman FG, Mariman EC, van Dieijen-Visser MP, Wodzig WK. Potential biomarkers for diagnosis of sarcoidosis using proteomics in serum. Respir Med 2007;101:1687–95. doi:10.1016/j.rmed.2007.03.002.PubMedCrossRef

28.

Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T. Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 1992;33:1972–80.PubMed

29.

Müller-Quernheim J. Sarcoidosis: immunopathogenetic concepts and their clinical application. Eur Respir J 1998;12:716–38. doi:10.1183/09031936.98.12030716.PubMedCrossRef

30.

Ainslie GM, Benatar SR. Serum angiotensin converting enzyme in sarcoidosis: sensitivity and specificity in diagnosis: correlations with disease activity, duration, extra-thoracic involvement, radiographic type and therapy. Q J Med 1985;55:253–70.PubMed

31.

Ina Y, Takada K, Sato T, Yamamoto M, Noda M, Morishita M. Soluble interleukin 2 receptors in patients with sarcoidosis. Possible origin. Chest 1992;102:1128–33. doi:10.1378/chest.102.4.1128.PubMedCrossRef

32.

Keicho N, Kitamura K, Takaku F, Yotsumoto H. Serum concentration of soluble interleukin-2 receptor as a sensitive parameter of disease activity in sarcoidosis. Chest 1990;98:1125–9. doi:10.1378/chest.98.5.1125.PubMedCrossRef

Title: 18F-FDG PET, genotype-corrected ACE and sIL-2R in newly diagnosed sarcoidosis
Authors: Ruth G. Keijsers
Fred J. Verzijlbergen
Wim J. Oyen
Jules M. van den Bosch
Henk J. Ruven
Heleen van Velzen-Blad
Jan C. Grutters
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 7/2009
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-009-1097-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

¹⁸F-FDG PET, genotype-corrected ACE and sIL-2R in newly diagnosed sarcoidosis

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 7/2009

Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

Improved quantification in single-pinhole and multiple-pinhole SPECT using micro-CT information

Steroid hormones affect binding of the sigma ligand 11C-SA4503 in tumour cells and tumour-bearing rats

2009 EANM parathyroid guidelines

Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

Can metamizol play a role in nuclear medicine practice?