Diagnostic efficiency of 68Ga-DOTATATE PET/CT as compared to 99mTc-Octreotide SPECT/CT and conventional morphologic modalities in neuroendocrine tumors

Document Type : Original Article


1 Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran


Objective(s): In view of somatostatin receptor (SSR) expression on cell membranes of the majority of neuroendocrine tumors (NETs), functional imaging exploiting analogs of SSR alongside the anatomical imaging is the mainstay of this diagnostic modality. In this prospective study, we assessed and directly compared the diagnostic parameters of 68Ga-DOTATATE PET/CT and 99mTc-Octreotide SPECT/CT, as well as CT/MRI.
Methods: Twenty-five NET patients, either histologically proven or highly suspicious for NET, who were referred for Octreotide Scan were enrolled in this prospective study. They all underwent 99mTc-Octreotide SPECT/CT and then 68Ga-DOTATATE PET/CT. A blind interpretation was conducted for each imaging as well as for the previously obtained conventional imaging (CT or MRI). The patient-based and lesion-based analysis were conducted and the results of the three modalities were compared. The histopathologic confirmation or follow-up data were considered as the gold standard. Also, the impact of 68Ga-DOTATATE PET/CT on the patient’s management was assessed.
Results: Overall, 77 lesions in 14 patients, 135 in 19 and 86 in 16 were detected on 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. On patient-based analysis, the sensitivity was 65%, 90% and 71% for 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. Also, the specificity was 80%, 80% and 75% for 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. The correlation between 68Ga-DOTATATE PET/CT and 99mTc-Octreotide SPECT/CT results was significant (P=0.02; kappa value=0.57), no correlation, however, was depicted with CI (P=0.07; kappa value=0.35). On lesion-based analysis, 68Ga-DOTATATE PET/CT found more organs (P=0.02) and lesions (P=0.001) in comparison with 99mTc-Octreotide SPECT/CT and also more lesions in comparison with CT/MRI (P=0.003). In addition, comparing with 99mTc-Octreotide SPECT/CT and CT/MRI, 68Ga-DOTATATE PET/CT revealed more data in 44% and 36% of the patients, resulting in management modification in 24% and 20%, respectively.
Conclusion: Comparing with 99mTc-Octreotide SPECT/CT and CT/MRI, 68Ga- DOTATATE PET/CT provided more sensitivity and specificity in patients with NETs showing more involved organs as well as tumoral lesions. Also, 68Ga-DOTATATE PET/ CT led to change of management in up to one-fourth of the patients, especially in a sub-group re-evaluated for recurrence.


Main Subjects

1. Deppen SA, Blume J, Bobbey AJ, Shah C, Graham MM, Lee P, et al. 68Ga-DOTATATE compared with 111In-DTPA-Octreotide and conventional imaging for pulmonary and gastroenteropancreatic neuroendocrine tumors: a systematic review and meta-analysis. J Nucl Med. 2016;57(6):872-8.
2. Deppen SA, Liu E, Blume JD, Clanton J, Shi C, Jones-Jackson LB, et al. Safety and efficacy of 68Ga- DOTATATE PET/CT for diagnosis, staging, and treatment management of neuroendocrine tumors. J Nucl Med. 2016;57(5):708-14.
3. Yang J, Kan Y, Ge BH, Yuan L, Li C, Zhao W. Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis. Acta Radiol. 2014;55(4):389-98.
4. Bodei L, Mueller-Brand J, Baum RP, Pavel ME, Hörsch D, O’Dorisio MS, et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2013;40(5):800-16.
5. Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017;3(10):1335-42.
6. Dromain C, Déandréis D, Scoazec JY, Goere D, Ducreux M, Baudin E, et al. Imaging of neuroendocrine tumors of the pancreas. Diagn Interv Imaging. 2016;97(12):1241-57.
7. Carreras C, Kulkarni HR, Baum RP. Rare metastases detected by (68)Ga-somatostatin receptor PET/CT in patients with neuroendocrine tumors. Recent Results Cancer Res. 2013;194:379-84.
8. 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.
9. Etchebehere EC, de Oliveira Santos A, Gumz B, Vicente A, Hoff PG, et al. 68Ga-DOTATATE PET/CT, 99mTc-HYNIC-octreotide SPECT/CT, and whole-body MR imaging in detection of neuroendocrine tumors: a prospective trial. J Nucl Med. 2014;55(10):1598- 604.
10. Virgolini I, Ambrosini V, Bomanji JB, Baum RP, Fanti S, Gabriel M, et al. Procedure guidelines for PET/ CT tumour imaging with 68 Ga-DOTA-conjugated peptides: 68 Ga-DOTA-TOC, 68 Ga-DOTA-NOC, 68 Ga-DOTA-TATE. Eur J Nucl Med Mol Imaging. 2010;37(10):2004-10.
11. Agrawal K, Esmail AA, Gnanasegaran G, Navalkissoor S, Mittal BR, Fogelman I. Pitfalls and limitations of radionuclide imaging in endocrinology. Semin Nucl Med. 2015;45(5):440-57.
12. Cherk MH, Kong G, Hicks RJ, Hofman MS. Changes in biodistribution on 68 Ga-DOTA-Octreotate PET/ CT after long acting somatostatin analogue therapy in neuroendocrine tumour patients may result in pseudoprogression. Cancer Imaging. 2018;18(1):3.
13. Bozkurt MF, Virgolini I, Balogova S, Beheshti M, Rubello D, Decristoforo C, et al. Guideline for PET/ CT imaging of neuroendocrine neoplasms with 68 Ga- DOTA-conjugated somatostatin receptor targeting peptides and 18 F–DOPA. Eur J Nucl Med Mol Imaging. 2017;44(9):1588-601.
14. Clarke BN. PET radiopharmaceuticals: what’s new, what’s reimbursed, and what’s next? J Nucl Med Technol. 2018;46(1):12-6.
15. Sadowski SM, Neychev V, Millo C, Shih J, Nilubol N, Herscovitch P, et al. Prospective study of 68Ga- DOTATATE positron emission tomography/computed tomography for detecting gastro-entero-pancreatic neuroendocrine tumors and unknown primary sites. J Clin Oncol. 2016;34(6):588-96.
16. Mojtahedi A, Thamake S, Tworowska I, Ranganathan D, Delpassand ES. The value of 68Ga-DOTATATE PET/ CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature. Am J Nucl Med Mol Imaging. 2014;4(5):426-34.
17. Norlén O, Montan H, Hellman P, Stålberg P, Sundin A. Preoperative 68 Ga-DOTA-somatostatin analog- PET/CT hybrid imaging increases detection rate of intra-abdominal small intestinal neuroendocrine tumor lesions. World J Surg. 2018;42(2):498-505.
18. 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.
19. Walker RC, Smith GT, Liu E, Moore B, Clanton J, Stabin M. Measured human dosimetry of 68Ga-DOTATATE. J Nucl Med. 2013;54(6):855-60.
20. Moradi F, Jamali M, Barkhodari A, Schneider B, Chin F, Quon A, et al. Spectrum of 68Ga-DOTA TATE uptake in patients with neuroendocrine tumors. Clin Nucl Med. 2016;41(6):e281-7.
21. Bangard M, Behe M, Guhlke S, Otte R, Bender H, Maecke H, et al. Detection of somatostatin receptor-positive tumours using the new 99m Tc-tricine- HYNIC-D-Phe 1-Tyr 3-octreotide: first results in patients and comparison with 111 In-DTPA-D-Phe 1-octreotide. Eur J Nucl Med. 2000;27(6):628-37.
22. Haidar M, Shamseddine A, Panagiotidis E, Jreige M, Mukherji D, Assi R, et al. The role of 68Ga-DOTA-NOC PET/CT in evaluating neuroendocrine tumors: real-world experience from two large neuroendocrine tumor centers. Nucl Med Commun. 2017;38(2):170-7.
23. Jacobsson H, Larsson P, Jonsson C, Jussing E, Grybäck P. Normal uptake of 68Ga-DOTA-TOC by the pancreas uncinate process mimicking malignancy at somatostatin receptor PET. Clin Nucl Med. 2012;37(4):362-5.
24. Kroiss A, Putzer D, Decristoforo C, Uprimny C, Warwitz B, Nilica B, et al. 68 Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT. Eur J Nucl Med Mol Imaging. 2013;40(4):514-23.
25. 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.
26. Krausz Y, Freedman N, Rubinstein R, Lavie E, Orevi M, Tshori S, et al. 68 Ga-DOTA-NOC PET/CT imaging of neuroendocrine tumors: comparison with 111 In- DTPA-Octreotide (OctreoScan®). Mol Imaging Biol. 2011;13(3):583-93.
27. Artiko V, Afgan A, Petrović J, Radović B, Petrović N, Vlajković M, et al. Evaluation of neuroendocrine tumors with 99mTc-EDDA/HYNIC TOC. Nucl Med Rev Cent East Eur. 2016;19(2):99-103.
28. Lodish M, Dagalakis U, Chen CC, Sinaii N, Whitcomb P, Aikin A, et al. (111)In-Octreotide scintigraphy for identification of metastatic medullary thyroid carcinoma in children and adolescents. J Clin Endocrinol Metab. 2012;97(2):E207-12.
29. Beheshti M, Langsteger W, Rezaee A. PET/ CT in cancer: an interdisciplinary approach to individualized imaging. 1st ed. Philadelphia: Elsevier Health Sciences; 2017.
30. Albanus DR, Apitzsch J, Erdem Z, Erdem O, Verburg F, Behrendt F, et al. Clinical value of 68Ga-DOTATATE-PET/CT compared to stand-alone contrast enhanced CT for the detection of extra-hepatic metastases in patients with neuroendocrine tumours (NET). Eur J Radio. 2015;84(10):1866-72.
31. 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.
32. Juchems M. Neuroendocrine tumors of the abdomen. Radiologe. 2018;58(1):36-44.
33. Kazmierczak PM, Rominger A, Wenter V, Spitzweg C, Auernhammer C, Angele MK, et al. The added value of 68 Ga-DOTA-TATE-PET to contrast-enhanced CT for primary site detection in CUP of neuroendocrine origin. Eur Radiol. 2017;27(4):1676-84.
34. Ruf J, Heuck F, Schiefer J, Denecke T, Elgeti F, Pascher A, et al. Impact of multiphase 68Ga-DOTATOC-PET/CT on therapy management in patients with neuroendocrine tumors. Neuroendocrinology. 2010;91(1):101-9.
35. 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.
36. Schraml C, Schwenzer NF, Sperling O, Aschoff P, Lichy MP, Müller M, et al. Staging of neuroendocrine tumours: comparison of [68Ga] DOTATOC multiphase PET/CT and whole-body MRI. Cancer Imaging. 2013;13(1):63-72.