Searching for primaries in patients with neuroendocrine tumors (NET) of unknown primary and clinically suspected NET: Evaluation of Ga-68 DOTATOC PET/CT and In-111 DTPA octreotide SPECT/CT

Nils Friedemann Schreiter 1 , Ann-Mirja Bartels 1 , Vera Froeling 2 , Ingo Steffen 1 , Ulrich-Frank Pape 3 , Alexander Beck 2 , Bernd Hamm 2 , Winfried Brenner 1 , and Rainer Röttgen 4
  • 1 Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
  • 2 Department of Radiology, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
  • 3 Department of Gastroenterology, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
  • 4 Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany / Department of Radiology, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany

Abstract

Background. To evaluate the clinical efficacy of In-111 DTPA octreotide SPECT/CT and Ga-68 DOTATOC PET/CT for detection of primary tumors in patients with either neuroendocrine tumor of unknown primary (NETUP) or clinically suspected primary NET (SNET).

Patients and methods. A total of 123 patients were included from 2006 to 2009, 52 received Ga-68 DOTATOC PET/CT (NETUP, 33; SNET, 19) and 71 underwent In-111 DTPA octreotide SPECT/CT (50; 21). The standard of reference included histopathology or clinical verification based on follow-up examinations.

Results. In the NETUP group Ga-68 DOTATOC detected primaries in 15 patients (45.5%) and In-111 DTPA octreotide in 4 patients (8%) (p < 0.001); in the SNET group, only 2 primaries could be detected, all by Ga-68 DOTATOC. In patients with NETUP, primary tumors could be found significantly more often than in patients with SNET (p = 0.01). Out of these 21 patients 14 patients were operated.

Conclusion. Ga-68 DOTATOC PET/CT is preferable to In-111 DTPA octreotide SPECT/CT when searching for primary NETs in patients with NETUP but should be used with caution in patients with SNET.

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  • 1 . Hoyer D, Bell GI, Berelowitz M, Epelbaum J, Feniuk W, Humphrey PP, et al. Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci 1995; 16: 86-8.

  • 2 . Janson ET, Sorbye H, Welin S, Federspiel B, Gronbaek H, Hellman P, et al. Nordic Guidelines 2010 for diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours. Acta Oncol 2010; 49: 740-56.

  • 3 . Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 2003; 24: 389-427.

  • 4 . Pape UF, Berndt U, Muller-Nordhorn J, Bohmig M, Roll S, Koch M, et al. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer 2008; 15: 1083-97.

  • 5 . Rindi G, Leiter AB, Kopin AS, Bordi C, Solcia E. The “normal” endocrine cell of the gut: changing concepts and new evidences. Ann N Y Acad Sci 2004; 1014: 1-12.

  • 6 . Hauso O, Gustafsson BI, Kidd M, Waldum HL, Drozdov I, Chan AK, et al. Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer 2008; 113: 2655-64.

  • 7 . Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003; 97: 934-59.

  • 8 . Kirshbom PM, Kherani AR, Onaitis MW, Feldman JM, Tyler DS. Carcinoids of unknown origin: comparative analysis with foregut, midgut, and hindgut carcinoids. Surgery 1998; 124: 1063-70.

  • 9 . Quaedvlieg PF, Visser O, Lamers CB, Janssen-Heijen ML, Taal BG. Epidemiology and survival in patients with carcinoid disease in The Netherlands. An epidemiological study with 2391 patients. Ann Oncol 2001; 12: 1295-300.

  • 10. Spigel DR, Hainsworth JD, Greco FA. Neuroendocrine carcinoma of unknown primary site. Semin Oncol 2009; 36: 52-9.

  • 11. Fendrich V, Bartsch DK. Surgical treatment of gastrointestinal neuroendocrine tumors. Langenbecks Arch Surg 2011; 396: 299-311.

  • 12. Fischer L, Mehrabi A, Buchler MW. Neuroendocrine tumors of the duodenum and pancreas. Surgical strategy. Chirurg 2011; 82: 583-90.

  • 13. Norton JA, Fraker DL, Alexander HR, Gibril F, Liewehr DJ, Venzon DJ, et al. Surgery increases survival in patients with gastrinoma. Ann Surg 2006; 244: 410-9.

  • 14. Plockinger U, Rindi G, Arnold R, Eriksson B, Krenning EP, de Herder WW, et al. Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology 2004; 80: 394-424.

  • 15. Sundin A, Vullierme MP, Kaltsas G, Plockinger U. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: radiological examinations. Neuroendocrinology 2009; 90: 167-83.

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

  • 17. Kowalski J, Henze M, Schuhmacher J, Macke HR, Hofmann M, Haberkorn U. Evaluation of positron emission tomography imaging using [68Ga]-DOTA-D Phe(1)-Tyr(3)-Octreotide in comparison to [111In]-DTPAOC SPECT. First results in patients with neuroendocrine tumors. Mol Imaging Biol 2003; 5: 42-8.

  • 18. Kwekkeboom D, Krenning EP, de Jong M. Peptide receptor imaging and therapy. J Nucl Med 2000; 41: 1704-13.

  • 19. 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: 853-8.

  • 20. Lebtahi R, Le Cloirec J, Houzard C, Daou D, Sobhani I, Sassolas G, et al. Detection of neuroendocrine tumors: 99mTc-P829 scintigraphy compared with 111In-pentetreotide scintigraphy. J Nucl Med 2002; 43: 889-95.

  • 21. Vick C, Zech CJ, Hopfner S, Waggershauser T, Reiser M. Imaging of neuroendocrine tumors of the pancreas. Radiologe 2003; 4: 293-300.

  • 22. Rambaldi PF, Cuccurullo V, Briganti V, Mansi L. The present and future role of (111)In pentetreotide in the PET era. Q J Nucl Med Mol Imaging 2005; 49: 225-35.

  • 23. 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: 1617-26.

  • 24. Hartmann H, Zophel K, Freudenberg R, Oehme L, Andreeff M, Wunderlich G, et al. [Radiation exposure of patients during 68Ga-DOTATOC PET/CT examinations]. Nuklearmedizin 2009; 48: 201-7.

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

  • 26. Fani M, Del Pozzo L, Abiraj K, Mansi R, Tamma ML, Cescato R, et al. PET of somatostatin receptor-positive tumors using 64Cu- and 68Ga-somatostatin antagonists: the chelate makes the difference. J Nucl Med 2011; 52: 1110-8.

  • 27. Toumpanakis C, Kim MK, Rinke A, Bergestuen DS, Thirlwell C, Khan MS, et al. Combination of cross-sectional and molecular imaging studies in the localization of gastroenteropancreatic neuroendocrine tumors. Neuroendocrinology 2014; DOI:10.1159/000358727

  • 28. Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA, et al. Processing of generator-produced 68Ga for medical application. J Nucl Med 2007; 48: 1741-8.

  • 29. Wang SC, Parekh JR, Zuraek MB, Venook AP, Bergsland EK, Warren RS, et al. Identification of unknown primary tumors in patients with neuroendocrine liver metastases. Arch Surg 2010; 145: 276-80.

  • 30. Givi B, Pommier SJ, Thompson AK, Diggs BS, Pommier RF. Operative resection of primary carcinoid neoplasms in patients with liver metastases yields significantly better survival. Surgery 2006; 140: 891-7.

  • 31. Hellman P, Lundstrom T, Ohrvall U, Eriksson B, Skogseid B, Oberg K, et al. Effect of surgery on the outcome of midgut carcinoid disease with lymph node and liver metastases. World J Surg 2002; 26: 991-7.

  • 32. Khashab MA, Yong E, Lennon AM, Shin EJ, Amateau S, Hruban RH, et al. EUS is still superior to multidetector computerized tomography for detection of pancreatic neuroendocrine tumors. Gastrointest Endosc 2011; 73: 691-6.

  • 33. Prasad V, Ambrosini V, Hommann M, Hoersch D, Fanti S, Baum RP. Detection of unknown primary neuroendocrine tumours (CUP-NET) using (68)Ga- DOTA-NOC receptor PET/CT. Eur J Nucl Med Mol Imaging 2010; 37: 67-77.

  • 34. Savelli G, Lucignani G, Seregni E, Marchiano A, Serafini G, Aliberti G, et al. Feasibility of somatostatin receptor scintigraphy in the detection of occult primary gastro-entero-pancreatic (GEP) neuroendocrine tumours. Nucl Med Commun 2004; 25: 445-9.

  • 35. Breeman WA, de Blois E, Sze Chan H, Konijnenberg M, Kwekkeboom DJ, Krenning EP. (68)Ga-labeled DOTA-peptides and (68)Ga-labeled radiopharmaceuticals for positron emission tomography: current status of research, clinical applications, and future perspectives. Semin Nucl Med 2011; 41: 314-21.

  • 36. Cimitan M, Buonadonna A, Cannizzaro R, Canzonieri V, Borsatti E, Ruffo R, et al. Somatostatin receptor scintigraphy versus chromogranin A assay in the management of patients with neuroendocrine tumors of different types: clinical role. Ann Oncol 2003; 14: 1135-41.

  • 37. Rodrigues M, Gabriel M, Heute D, Putzer D, Griesmacher A, Virgolini I. Concordance between results of somatostatin receptor scintigraphy with 111In-DOTA-DPhe 1-Tyr 3-octreotide and chromogranin A assay in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2008; 35: 1796-802.

  • 38. Stoyianni A, Pentheroudakis G, Pavlidis N. Neuroendocrine carcinoma of unknown primary: a systematic review of the literature and a comparative study with other neuroendocrine tumors. Cancer Treat Rev 2011; 37: 358-65.

  • 39. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 2010; 39: 707-12.

  • 40. 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: 458-67.

  • 41. 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 triplephase protocol. J Nucl Med 2011; 52: 697-704.

  • 42. Berge T, Linell F. Carcinoid tumours. Frequency in a defined population during a 12-year period. Acta Pathol Microbiol Scand A 1976; 84: 322-30.

  • 43. Katona TM, Jones TD, Wang M, Abdul-Karim FW, Cummings OW, Cheng L. Molecular evidence for independent origin of multifocal neuroendocrine tumors of the enteropancreatic axis. Cancer Res 2006; 66: 4936-42.

  • 44. Saha S, Hoda S, Godfrey R, Sutherland C, Raybon K. Carcinoid tumors of the gastrointestinal tract: a 44-year experience. South Med J 1989; 82: 1501-5.

  • 45. Watson RG, Johnston CF, O’Hare MM, Anderson JR, Wilson BG, Collins JS, et al. The frequency of gastrointestinal endocrine tumours in a well-defined population--Northern Ireland 1970-1985. Q J Med 1989; 72: 647-57.

  • 46. Fischer L, Kleeff J, Esposito I, Hinz U, Zimmermann A, Friess H, et al. Clinical outcome and long-term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas. Br J Surg 2008; 95: 627-35.

  • 47. O’Toole D, Salazar R, Falconi M, Kaltsas G, Couvelard A, de Herder WW, et al. Rare functioning pancreatic endocrine tumors. Neuroendocrinology 2006; 84: 189-95.

  • 48. Arnold R. Endocrine tumours of the gastrointestinal tract. Introduction: definition, historical aspects, classification, staging, prognosis and therapeutic options. Best Pract Res Clin Gastroenterol 2005; 19: 491-505.

  • 49. Dralle H, Krohn SL, Karges W, Boehm BO, Brauckhoff M, Gimm O. Surgery of resectable nonfunctioning neuroendocrine pancreatic tumors. World J Surg 2004; 28: 1248-60.

  • 50. Schurr PG, Strate T, Rese K, Kaifi JT, Reichelt U, Petri S, et al. Aggressive surgery improves long-term survival in neuroendocrine pancreatic tumors: an institutional experience. Ann Surg 2007; 245: 273-81.

  • 51. Vagefi PA, Razo O, Deshpande V, McGrath DJ, Lauwers GY, Thayer SP, et al. Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms: the Massachusetts General Hospital experience from 1977 to 2005. Arch Surg 2007; 142: 347-54.

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