Neuroendocrine Tumor Recurrence: Diagnosis with 68Ga-DOTATATE PET/CT

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In the follow-up of patients after curative resection of a neuroendocrine tumor, 68Ga-DOTATATE PET/CT is accurate, thus substantiating its use in clinical routine diagnostic imaging.


To evaluate diagnostic performance of gallium 68–tetraazacyclododecane tetraacetic acid–octreotate (68Ga-DOTATATE) in detection of recurrent neuroendocrine tumors (NETs).

Materials and Methods

Approval was waived by the local ethics committee for this retrospective study. Between 2007 and 2011, 63 patients (mean age, 58 years) were examined with 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) after primary NET curative resection. Reasons for PET/CT were regular follow-up examinations (n = 30), increased plasma levels of tumor markers (n = 27), or clinical suspicion of recurrence (n = 6). Final diagnosis was determined with histopathologic verification (n = 25) or clinical follow-up (n = 38). PET/CT scans were evaluated in consensus by two readers without blinding to clinical information and independently by two readers with blinding. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.


Final diagnosis of NET recurrence was determined in 29 patients. In three other patients, tumors of nonneuroendocrine origin were diagnosed. 68Ga-DOTATATE PET/CT helped identify NET recurrence in 26 of 29 patients (sensitivity, 90%) and exclude presence of recurrent NET in 28 of 34 patients (specificity, 82% ). PET/CT provided false-positive and false-negative results in six and three patients (PPV, 81% [26 of 32]; NPV, 90% [28 of 31]; accuracy, 86% [54 of 63]). In gastroenteropancreatic NET (n = 45), sensitivity was 94% (17 of 18); specificity was 89% (24 of 27); PPV was 85% (17 of 20); NPV was 96% (24 of 25); and accuracy was 91% (41 of 45). Two blinded readers achieved sensitivity of 79% (23 of 29) and 76% (22 of 29); specificity of 85% (29 of 34) and 94% (32 of 34) (κ = 0.80); and accuracy of 83% and 86%.


68Ga-DOTATATE PET/CT is accurate in detection of recurrent NET. Blinded PET/CT review markedly decreased sensitivity, underlining importance of considering clinical parameters in NET recurrence. Present results must be further validated to substantiate use of 68Ga-DOTATATE PET/CT in routine follow-up after curative resection of NET.

© RSNA, 2013

Online supplemental material is available for this article.


  • 1. Yao JC, Hassan M, Phan A, 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):3063–3072.
  • 2. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97(4):934–959.
  • 3. Boninsegna L, Panzuto F, Partelli S, et al. Malignant pancreatic neuroendocrine tumour: lymph node ratio and Ki67 are predictors of recurrence after curative resections. Eur J Cancer 2012;48(11):1608–1615.
  • 4. Welin S, Stridsberg M, Cunningham J, et al. Elevated plasma chromogranin A is the first indication of recurrence in radically operated midgut carcinoid tumors. Neuroendocrinology 2009;89(3):302–307.
  • 5. Pape UF, Perren A, Niederle B, et al. ENETS Consensus Guidelines for the management of patients with neuroendocrine neoplasms from the jejuno-ileum and the appendix including goblet cell carcinomas. Neuroendocrinology 2012;95(2):135–156.
  • 6. Arnold R, Chen YJ, Costa F, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: follow-up and documentation. Neuroendocrinology 2009;90(2):227–233.
  • 7. Vinik AI, Woltering EA, Warner RR, et al. NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas 2010;39(6):713–734.
  • 8. Falconi M, Bartsch DK, Eriksson B, et al. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. Neuroendocrinology 2012;95(2):120–134.
  • 9. Sundin A, Vullierme MP, Kaltsas G, Plöckinger U; Mallorca Consensus Conference participants; European Neuroendocrine Tumor Society. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: radiological examinations. Neuroendocrinology 2009;90(2):167–183.
  • 10. Kwekkeboom DJ, Krenning EP, Scheidhauer K, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: somatostatin receptor imaging with (111)In-pentetreotide. Neuroendocrinology 2009;90(2):184–189.
  • 11. Haug AR, Assmann G, Rist C, et al. Quantification of immunohistochemical expression of somatostatin receptors in neuroendocrine tumors using 68Ga-DOTATATE PET/CT [in German]. Radiologe 2010;50(4):349–354.
  • 12. Haug A, Auernhammer CJ, Wängler 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):765–770.
  • 13. Ruf J, Heuck F, Schiefer J, et al. Impact of multiphase 68Ga-DOTATOC-PET/CT on therapy management in patients with neuroendocrine tumors. Neuroendocrinology 2010;91(1):101–109.
  • 14. Ruf J, Schiefer J, Furth C, 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.
  • 15. Haug AR, Auernhammer CJ, Wängler B, et al. 68Ga-DOTATATE PET/CT for the early prediction of response to somatostatin receptor-mediated radionuclide therapy in patients with well-differentiated neuroendocrine tumors. J Nucl Med 2010;51(9):1349–1356.
  • 16. Buchmann I, Henze M, Engelbrecht S, 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):1617–1626.
  • 17. Haug AR, Cindea-Drimus R, Auernhammer CJ, et al. The role of 68Ga-DOTATATE PET/CT in suspected neuroendocrine tumors. J Nucl Med 2012;53(11):1686–1692.
  • 18. Kumar R, Sharma P, Garg P, et al. Role of (68)Ga-DOTATOC PET-CT in the diagnosis and staging of pancreatic neuroendocrine tumours. Eur Radiol 2011;21(11):2408–2416.
  • 19. Naswa N, Sharma P, Kumar A, 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):1221–1228.
  • 20. Breeman WA, de Jong M, de Blois E, Bernard BF, Konijnenberg M, Krenning EP. Radiolabelling DOTA-peptides with 68Ga. Eur J Nucl Med Mol Imaging 2005;32(4):478–485.
  • 21. Kayani I, Conry BG, Groves AM, et al. A comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in pulmonary neuroendocrine tumors. J Nucl Med 2009;50(12):1927–1932.
  • 22. Virgolini I, Ambrosini V, Bomanji JB, 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):2004–2010.
  • 23. 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):40–47.
  • 24. Arnold R, Wilke A, Rinke A, et al. Plasma chromogranin A as marker for survival in patients with metastatic endocrine gastroenteropancreatic tumors. Clin Gastroenterol Hepatol 2008;6(7):820–827.
  • 25. Modlin IM, Gustafsson BI, Moss SF, Pavel M, Tsolakis AV, Kidd M, Chromogranin A: biological function and clinical utility in neuro endocrine tumor disease. Ann Surg Oncol 2010;17(9):2427–2443.
  • 26. Frilling A, Sotiropoulos GC, Radtke A, 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):850–856.
  • 27. Gabriel M, Decristoforo C, Kendler D, et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 2007;48(4):508–518.
  • 28. Putzer D, Gabriel M, Henninger B, 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):1214–1221.
  • 29. Narayanan P, Sohaib SA, Sahdev A, Rockall AG, Reznek RH. MR imaging of small adnexal masses [abstr]. Cancer Imaging 2010;10(A):S125.
  • 30. Boudreaux JP, Klimstra DS, Hassan MM, et al. The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the jejunum, ileum, appendix, and cecum. Pancreas 2010;39(6):753–766.
  • 31. Krausz Y, Rubinstein R, Appelbaum L, et al. Ga-68 DOTA-NOC uptake in the pancreas: pathological and physiological patterns. Clin Nucl Med 2012;37(1):57–62.

Article History

Received November 9, 2012; revision requested December 28; final revision received March 6, 2013; accepted April 1; final version accepted July 19.
Published online: Feb 2014
Published in print: Feb 2014