Skip to main content
Log in

Somatostatin receptor PET/CT in neuroendocrine tumours: update on systematic review and meta-analysis

  • Review Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Neuroendocrine tumours (NET) are uncommon and may be localized in many different places in the body. Traditional imaging has mainly been performed with CT and somatostatin receptor scintigraphy (SRS). Recently, it has become possible to use somatostatin receptor PET/CT (SMSR PET) instead, which might improve diagnostic quality. To evaluate the diagnostic quality of SMSR PET we performed a meta-analysis as an update of a previous study published in 2012.

Methods

A literature search was performed searching MEDLINE, Embase and five other databases with a combination of the expressions “PET”, “positron emission tomography”, “neuroendocrine” and “NET”. The search was updated to 31 December 2012. Studies were selected which evaluated the sensitivity and specificity of SMSR PET for NET in the thorax or abdomen with a study size of at least eight patients. The methodological quality of the included studies was evaluated with QUADAS-2.

Results

Eight studies fulfilled the inclusion criteria and were selected for final analysis, and 14 articles from a previous meta-analysis were added for a total of 22 articles. A total of 2,105 patients were included in the studies, an increase from 567 in the previous meta-analysis. The pooled sensitivity was 93 % (95 % CI 91 – 94 %) and specificity 96 % (95 % CI 95 – 98 %). The area under the summary ROC curve was 0.98 (95 % CI 0.95 – 1.0). In the previous meta-analysis the pooled sensitivity was 93 % (95 % CI 91 – 95 %) and specificity 91 % (95 % CI 82 – 97 %).

Conclusion

SMSR PET has good diagnostic performance for evaluation of NET in the thorax and abdomen, better than SRS which has been the previous standard method. This meta-analysis gives further support for switching to SMSR PET.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063–72. doi:10.1200/jco.2007.15.4377.

    Article  PubMed  Google Scholar 

  2. Vinik AI, Woltering EA, Warner RR, Caplin M, O’Dorisio TM, Wiseman GA, et al. NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 2010;39(6):713–34. doi:10.1097/MPA.0b013e3181ebaffd.

    Article  PubMed  Google Scholar 

  3. Salazar R, Wiedenmann B, Rindi G, Ruszniewski P. ENETS 2011 consensus guidelines for the management of patients with digestive neuroendocrine tumors: an update. Neuroendocrinology. 2012;95(2):71–3. doi:10.1159/000335600.

    Article  PubMed  CAS  Google Scholar 

  4. Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman WA, Kooij PP, Oei HY, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med. 1993;20(8):716–31.

    Article  PubMed  CAS  Google Scholar 

  5. Hofman MS, Kong G, Neels OC, Eu P, Hong E, Hicks RJ. High management impact of Ga-68 DOTATATE (GaTate) PET/CT for imaging neuroendocrine and other somatostatin expressing tumours. J Med Imaging Radiat Oncol. 2012;56(1):40–7. doi:10.1111/j.1754-9485.2011.02327.x.

    Article  PubMed  Google Scholar 

  6. Schreiter NF, Brenner W, Nogami M, Buchert R, Huppertz A, Pape UF, et al. Cost comparison of 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT for staging enteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2012;39(1):72–82. doi:10.1007/s00259-011-1935-5.

    Article  PubMed  Google Scholar 

  7. Treglia G, Castaldi P, Rindi G, Giordano A, Rufini V. Diagnostic performance of gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis. Endocrine. 2012;42(1):80–7. doi:10.1007/s12020-012-9631-1.

    Article  PubMed  CAS  Google Scholar 

  8. SBU. Utvärdering av metoder i hälso- och sjukvården: En handbok. Version 2013-02-22. Stockholm: Statens beredning för medicinsk utvärdering (SBU); 2013.

  9. Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007;7:10. doi:10.1186/1471-2288-7-10.

    Article  PubMed  Google Scholar 

  10. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529–36. doi:10.1059/0003-4819-155-8-201110180-00009.

    Article  PubMed  Google Scholar 

  11. Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol. 2006;6:31. doi:10.1186/1471-2288-6-31.

    Article  PubMed  Google Scholar 

  12. Sterne JAC, Egger M, Smith GD. Investigating and dealing with publication and other biases. In: Egger M, Smith GD, Altman DG, editors. Systematic reviews in health care: meta-analysis in context. London: BMJ Publishing Group; 2001. p. 189–208.

    Chapter  Google Scholar 

  13. Putzer D, Gabriel M, Henninger B, Kendler D, Uprimny C, Dobrozemsky G, et al. Bone metastases in patients with neuroendocrine tumor: 68Ga-DOTA-Tyr3-octreotide PET in comparison to CT and bone scintigraphy. J Nucl Med. 2009;50(8):1214–21. doi:10.2967/jnumed.108.060236.

    Article  PubMed  Google Scholar 

  14. Ambrosini V, Campana D, Tomassetti P, Fanti S. 68Ga-labelled peptides for diagnosis of gastroenteropancreatic NET. Eur J Nucl Med Mol Imaging. 2012;39 Suppl 1:S52–60. doi:10.1007/s00259-011-1989-4.

    Article  PubMed  Google Scholar 

  15. Buchmann I, Henze M, Engelbrecht S, Eisenhut M, Runz A, Schafer M, et al. Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2007;34(10):1617–26. doi:10.1007/s00259-007-0450-1.

    Article  PubMed  CAS  Google Scholar 

  16. Frilling A, Sotiropoulos GC, Radtke A, Malago M, Bockisch A, Kuehl H, et al. The impact of 68Ga-DOTATOC positron emission tomography/computed tomography on the multimodal management of patients with neuroendocrine tumors. Ann Surg. 2010;252(5):850–6. doi:10.1097/SLA.0b013e3181fd37e8.

    Article  PubMed  Google Scholar 

  17. Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med. 2007;48(4):508–18.

    Article  PubMed  CAS  Google Scholar 

  18. Haug A, Auernhammer CJ, Wangler B, Tiling R, Schmidt G, Goke B, et al. Intraindividual comparison of 68Ga-DOTA-TATE and 18F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2009;36(5):765–70. doi:10.1007/s00259-008-1030-8.

    Article  PubMed  CAS  Google Scholar 

  19. Haug AR, Cindea-Drimus R, Auernhammer CJ, Reincke M, Wangler B, Uebleis C, et al. The role of 68Ga-DOTATATE PET/CT in suspected neuroendocrine tumors. J Nucl Med. 2012;53(11):1686–92. doi:10.2967/jnumed.111.101675.

    Article  PubMed  CAS  Google Scholar 

  20. Hofmann M, Maecke H, Borner R, Weckesser E, Schoffski P, Oei L, et al. Biokinetics and imaging with the somatostatin receptor PET radioligand 68Ga-DOTATOC: preliminary data. Eur J Nucl Med. 2001;28(12):1751–7. doi:10.1007/s002590100639.

    Article  PubMed  CAS  Google Scholar 

  21. Jindal T, Kumar A, Venkitaraman B, Dutta R, Kumar R. Role of 68Ga-DOTATOC PET/CT in the evaluation of primary pulmonary carcinoids. Korean J Intern Med. 2010;25(4):386–91. doi:10.3904/kjim.2010.25.4.386.

    Article  PubMed  Google Scholar 

  22. Kabasakal L, Demirci E, Ocak M, Decristoforo C, Araman A, Ozsoy Y, et al. Comparison of 68Ga-DOTATATE and 68Ga-DOTANOC PET/CT imaging in the same patient group with neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2012;39(8):1271–7. doi:10.1007/s00259-012-2123-y.

    Article  PubMed  Google Scholar 

  23. Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG. Cancer. 2008;112(11):2447–55. doi:10.1002/cncr.23469.

    Article  PubMed  Google Scholar 

  24. Kayani I, Conry BG, Groves AM, Win T, Dickson J, Caplin M, et al. A comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in pulmonary neuroendocrine tumors. J Nucl Med. 2009;50(12):1927–32. doi:10.2967/jnumed.109.066639.

    Article  PubMed  Google Scholar 

  25. Koukouraki S, Strauss LG, Georgoulias V, Schuhmacher J, Haberkorn U, Karkavitsas N, et al. Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy. Eur J Nucl Med Mol Imaging. 2006;33(4):460–6. doi:10.1007/s00259-005-0006-1.

    Article  PubMed  CAS  Google Scholar 

  26. Krausz Y, Freedman N, Rubinstein R, Lavie E, Orevi M, Tshori S, et al. 68Ga-DOTA-NOC PET/CT imaging of neuroendocrine tumors: comparison with 111In-DTPA-octreotide (OctreoScan®). Mol Imaging Biol. 2011;13(3):583–93. doi:10.1007/s11307-010-0374-1.

    Article  PubMed  Google Scholar 

  27. Kumar R, Sharma P, Garg P, Karunanithi S, Naswa N, Sharma R, et al. Role of 68Ga-DOTATOC PET-CT in the diagnosis and staging of pancreatic neuroendocrine tumours. Eur Radiol. 2011;21(11):2408–16. doi:10.1007/s00330-011-2199-y.

    Article  PubMed  Google Scholar 

  28. Mayerhoefer ME, Schuetz M, Magnaldi S, Weber M, Trattnig S, Karanikas G. Are contrast media required for (68)Ga-DOTATOC PET/CT in patients with neuroendocrine tumours of the abdomen? Eur Radiol. 2012;22(4):938–46. doi:10.1007/s00330-011-2328-7.

    Article  PubMed  Google Scholar 

  29. Naswa N, Sharma P, Kumar A, Nazar AH, Kumar R, Chumber S, et al. Gallium-68-DOTA-NOC PET/CT of patients with gastroenteropancreatic neuroendocrine tumors: a prospective single-center study. AJR Am J Roentgenol. 2011;197(5):1221–8. doi:10.2214/ajr.11.7298.

    Article  PubMed  Google Scholar 

  30. Pfeifer A, Knigge U, Mortensen J, Oturai P, Berthelsen AK, Loft A, et al. Clinical PET of neuroendocrine tumors using 64Cu-DOTATATE: first-in-humans study. J Nucl Med. 2012;53(8):1207–15. doi:10.2967/jnumed.111.101469.

    Article  PubMed  CAS  Google Scholar 

  31. Ruf J, Schiefer J, Furth C, Kosiek O, Kropf S, Heuck F, et al. 68Ga-DOTATOC PET/CT of neuroendocrine tumors: spotlight on the CT phases of a triple-phase protocol. J Nucl Med. 2011;52(5):697–704. doi:10.2967/jnumed.110.083741.

    Article  PubMed  Google Scholar 

  32. Srirajaskanthan R, Kayani I, Quigley AM, Soh J, Caplin ME, Bomanji J. The role of 68Ga-DOTATATE PET in patients with neuroendocrine tumors and negative or equivocal findings on 111In-DTPA-octreotide scintigraphy. J Nucl Med. 2010;51(6):875–82. doi:10.2967/jnumed.109.066134.

    Article  PubMed  CAS  Google Scholar 

  33. Versari A, Camellini L, Carlinfante G, Frasoldati A, Nicoli F, Grassi E, et al. Ga-68 DOTATOC PET, endoscopic ultrasonography, and multidetector CT in the diagnosis of duodenopancreatic neuroendocrine tumors: a single-centre retrospective study. Clin Nucl Med. 2010;35(5):321–8. doi:10.1097/RLU.0b013e3181d6677c.

    Article  PubMed  Google Scholar 

  34. Froeling V, Elgeti F, Maurer MH, Scheurig-Muenkler C, Beck A, Kroencke TJ, et al. Impact of Ga-68 DOTATOC PET/CT on the diagnosis and treatment of patients with multiple endocrine neoplasia. Ann Nucl Med. 2012;26(9):738–43. doi:10.1007/s12149-012-0634-z.

    Article  PubMed  CAS  Google Scholar 

  35. Schreiter NF, Nogami M, Steffen I, Pape UF, Hamm B, Brenner W, et al. Evaluation of the potential of PET-MRI fusion for detection of liver metastases in patients with neuroendocrine tumours. Eur Radiol. 2012;22(2):458–67. doi:10.1007/s00330-011-2266-4.

    Article  PubMed  Google Scholar 

  36. Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumors. Semin Nucl Med. 2006;36(3):228–47. doi:10.1053/j.semnuclmed.2006.03.007.

    Article  PubMed  Google Scholar 

  37. Lebtahi R, Cadiot G, Sarda L, Daou D, Faraggi M, Petegnief Y, et al. Clinical impact of somatostatin receptor scintigraphy in the management of patients with neuroendocrine gastroenteropancreatic tumors. J Nucl Med. 1997;38(6):853–8.

    PubMed  CAS  Google Scholar 

  38. Gibril F, Reynolds JC, Doppman JL, Chen CC, Venzon DJ, Termanini B, et al. Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. A prospective study. Ann Intern Med. 1996;125(1):26–34.

    Article  PubMed  CAS  Google Scholar 

  39. Chiti A, Fanti S, Savelli G, Romeo A, Bellanova B, Rodari M, et al. Comparison of somatostatin receptor imaging, computed tomography and ultrasound in the clinical management of neuroendocrine gastro-entero-pancreatic tumours. Eur J Nucl Med. 1998;25(10):1396–403.

    Article  PubMed  CAS  Google Scholar 

  40. Shi W, Johnston CF, Buchanan KD, Ferguson WR, Laird JD, Crothers JG, et al. Localization of neuroendocrine tumours with [111In] DTPA-octreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging. QJM. 1998;91(4):295–301.

    Article  PubMed  CAS  Google Scholar 

  41. de Kerviler E, Cadiot G, Lebtahi R, Faraggi M, Le Guludec D, Mignon M. Somatostatin receptor scintigraphy in forty-eight patients with the Zollinger-Ellison syndrome. GRESZE: Groupe d’Etude du Syndrome de Zollinger-Ellison. Eur J Nucl Med. 1994;21(11):1191–7.

    Article  PubMed  Google Scholar 

  42. Termanini B, Gibril F, Reynolds JC, Doppman JL, Chen CC, Stewart CA, et al. Value of somatostatin receptor scintigraphy: a prospective study in gastrinoma of its effect on clinical management. Gastroenterology. 1997;112(2):335–47.

    Article  PubMed  CAS  Google Scholar 

  43. Zimmer T, Stolzel U, Bader M, Koppenhagen K, Hamm B, Buhr H, et al. Endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localisation of insulinomas and gastrinomas. Gut. 1996;39(4):562–8.

    Article  PubMed  CAS  Google Scholar 

  44. Cadiot G, Lebtahi R, Sarda L, Bonnaud G, Marmuse JP, Vissuzaine C, et al. Preoperative detection of duodenal gastrinomas and peripancreatic lymph nodes by somatostatin receptor scintigraphy. Groupe D’etude Du Syndrome De Zollinger-Ellison. Gastroenterology. 1996;111(4):845–54.

    Article  PubMed  CAS  Google Scholar 

  45. Alexander HR, Fraker DL, Norton JA, Bartlett DL, Tio L, Benjamin SB, et al. Prospective study of somatostatin receptor scintigraphy and its effect on operative outcome in patients with Zollinger-Ellison syndrome. Ann Surg. 1998;228(2):228–38.

    Article  PubMed  CAS  Google Scholar 

  46. Mariani G, Bruselli L, Kuwert T, Kim EE, Flotats A, Israel O, et al. A review on the clinical uses of SPECT/CT. Eur J Nucl Med Mol Imaging. 2010;37(10):1959–85. doi:10.1007/s00259-010-1390-8.

    Article  PubMed  Google Scholar 

  47. Lu SJ, Gnanasegaran G, Buscombe J, Navalkissoor S. Single photon emission computed tomography/computed tomography in the evaluation of neuroendocrine tumours: a review of the literature. Nucl Med Commun. 2013;34(2):98–107. doi:10.1097/MNM.0b013e32835bd59d.

    Article  PubMed  Google Scholar 

  48. Ambrosini V, Campana D, Bodei L, Nanni C, Castellucci P, Allegri V, et al. 68Ga-DOTANOC PET/CT clinical impact in patients with neuroendocrine tumors. J Nucl Med. 2010;51(5):669–73. doi:10.2967/jnumed.109.071712.

    Article  PubMed  Google Scholar 

  49. Virgolini I, Ambrosini V, Bomanji JB, Baum RP, Fanti S, Gabriel M, et al. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE. Eur J Nucl Med Mol Imaging. 2010;37(10):2004–10. doi:10.1007/s00259-010-1512-3.

    Article  PubMed  Google Scholar 

  50. Naswa N, Sharma P, Nazar AH, Agarwal KK, Kumar R, Ammini AC, et al. Prospective evaluation of 68Ga-DOTA-NOC PET-CT in phaeochromocytoma and paraganglioma: preliminary results from a single centre study. Eur Radiol. 2012;22(3):710–9. doi:10.1007/s00330-011-2289-x.

    Article  PubMed  Google Scholar 

  51. Sundin A, Garske U, Orlefors H. Nuclear imaging of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2007;21(1):69–85. doi:10.1016/j.beem.2006.12.003.

    Article  PubMed  CAS  Google Scholar 

  52. Ambrosini V, Tomassetti P, Castellucci P, Campana D, Montini G, Rubello D, et al. Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours. Eur J Nucl Med Mol Imaging. 2008;35(8):1431–8. doi:10.1007/s00259-008-0769-2.

    Article  PubMed  CAS  Google Scholar 

  53. Koopmans KP, Neels OC, Kema IP, Elsinga PH, Sluiter WJ, Vanghillewe K, et al. Improved staging of patients with carcinoid and islet cell tumors with 18F-dihydroxy-phenyl-alanine and 11C-5-hydroxy-tryptophan positron emission tomography. J Clin Oncol. 2008;26(9):1489–95. doi:10.1200/jco.2007.15.1126.

    Article  PubMed  Google Scholar 

  54. Poeppel TD, Binse I, Petersenn S, Lahner H, Schott M, Antoch G, et al. 68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors. J Nucl Med. 2011;52(12):1864–70. doi:10.2967/jnumed.111.091165.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Margareta Landin, head of the Medical Library, Örebro University Hospital, for help with the literature searches.

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Håkan Geijer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Geijer, H., Breimer, L.H. Somatostatin receptor PET/CT in neuroendocrine tumours: update on systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 40, 1770–1780 (2013). https://doi.org/10.1007/s00259-013-2482-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-013-2482-z

Keywords

Navigation