Radiolabeled Somatostatin Analogues in the Treatment of Non-GEP-NET Tumors

  • Annibale Versari
  • Angelina Filice
  • Massimiliano Casali
  • Martina Sollini
  • Andrea Frasoldati


In the last two decades Peptide Receptor Radionuclide Therapy (PRRT) has acquired great importance as an alternative or complementary tool in the treatment of neuroendocrine tumors (NETs) and other somatostatin receptor (SSTR) positive tumors. Many experiences of PRRT using different radiopharmaceuticals, mainly beta-emitters 90Yttrium (90Y) and 177Lutetium (177Lu) labeled peptides, are reported in the literature with encouraging results in terms of tumor regression, self-assessed quality of life, and overall survival. SSTRs are mainly expressed in Gastro-Entero-Pancreatic neuroendocrine tumors (GEP-NETs) but in many other neoplasms (NETs and non-NETs) it is possible to find a high SSTR expression. Some of these are pheochromocytoma/paraganglioma, bronchial NET, thymic NET, meningioma, thyroid cancer (differentiated and medullary) and Merkel cell carcinoma.

Theranostics (therapy and diagnosis) using radiolabeled somatostatin analogues has proved to be a valuable tool in the management of SSTR-expressing tumors. Many studies are available for PRRT in GEP-NETs demonstrating very interesting results. Other neoplasms with SSTR expression can be evaluated and treated according to the same rationale: the experience is limited but sometimes promising. Further studies are necessary to confirm these interesting results.


PRRT Neuroendocrine tumors Somatostatin receptors Pheochromocytoma/paraganglioma Meningioma Bronchial NETs Thyroid cancer Thymic NETs 90Y/177Lu-labeled somatostatin analogues STTR imaging Theranostics 



The authors thank Chiara Coruzzi for the contribution in reference research and proof correction.


  1. 1.
    Sollini M, Boni R, Traino AC, Lazzeri E, Pasqualetti F, Modeo L, Mariani G, Petrini M, Erba PA. New approaches for imaging and therapy of solid cancer. Q J Nucl Med Mol Imaging. 2015;59:168–83.PubMedGoogle Scholar
  2. 2.
    Kowalski J, Henze M, Schuhmacher J, Maecke HR, Hofmann M, Haberkorn U. Evaluation of positron emission tomography imaging using [68Ga]-DOTA-D-Phe1-Tyr3-octreotide in comparison to [111In]-DTPAOC SPECT. First results in patients with neuroendocrine tumors. Mol Imaging Biol. 2003;5:42–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Buchmann I, Henze M, Engelbrecht S, Eisenhut M, Runz A, Schäfer 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.CrossRefPubMedGoogle Scholar
  4. 4.
    Sollini M, Erba PA, Fraternali A, Casali M, Di Paolo ML, Froio A, Frasoldati A, Versari A. PET and PET/CT with 68gallium-labeled somatostatin analogues in non GEP-NETs tumors. Sci World J. 2014;2014:194123. Scholar
  5. 5.
    Hofmann M, Maecke H, Börner R, Weckesser E, Schöffski 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(12):1751–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Wild D, Schmitt JS, Ginj M, Mäcke HR, Bernard BF, Krenning E, et al. DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals. Eur J Nucl Med Mol Imaging. 2003;30(10):1338–47.CrossRefPubMedGoogle Scholar
  7. 7.
    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.CrossRefPubMedGoogle Scholar
  8. 8.
    Antunes P, Ginj M, Zhang H, Waser B, Baum RP, Reubi JC, et al. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals? Eur J Nucl Med Mol Imaging. 2007;34(7):982–93.CrossRefPubMedGoogle Scholar
  9. 9.
    Ambrosini V, Campana D, Tomassetti P, Grassetto G, Rubello D, Fanti S. PET/CT with 68Gallium-DOTA-peptides in NET: an overview. Eur J Radiol. 2011;80:e116–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Smith-Jones PM, Bischof C, Leimer M, Gludovacz D, Angelberger P, Pangerl T, et al. DOTA-lanreotide: a novel somatostatin analog for tumor diagnosis and therapy. Endocrinology. 1999;140:5136–48.CrossRefPubMedGoogle Scholar
  11. 11.
    Virgolini I, Szilvasi I, Kurtaran A, Angelberger P, Raderer M, Havlik E, Vorbeck F, Bischof C, Leimer M, Dorner G, Kletter K, Niederle B, Scheithauer W. Smith-Jones P.111In-DOTA-lanreotide: biodistribution, safety and radiation absorbed dose in tumor patients. J Nucl Med. 1998;39:1928–36.PubMedGoogle Scholar
  12. 12.
    Reubi JC, Schär JC, Waser B, Wenger S, Heppeler A, Schmitt JS, Mäcke HR. Affinity profiles for human somatostatin receptor subtypes SST1-SSt5 of somatostatinradiotracer selected for scintigraphic and radiothaerpeutic and radio therapeutic use. Eur J Nucl Med. 2000;27:273–82.CrossRefPubMedGoogle Scholar
  13. 13.
    Vrachimis A, Stegger L, Wenning C, Noto B, Burg MC, Konnert JR, Allkemper T, Heindel W, Riemann B, Schäfers M. Weckesser M.[(68)Ga]DOTATATE PET/MRI and [(18)F]FDG PET/CT are complementary and superior to diffusion-weighted MR imaging for radioactive-iodine-refractory differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2016;43(10):1765–72. Scholar
  14. 14.
    Afshar-Oromieh A, Wolf MB, Kratochwil C, Giesel FL, Combs SE, Dimitrakopoulou-Strauss A, Gnirs R, Roethke MC, Schlemmer HP, Haberkorn U. Comparison of 68Ga-DOTATOC-PET/CT and PET/MRI hybrid systems in patients with cranial meningioma: initial results. Neuro-Oncology. 2015;17(2):312–9. Scholar
  15. 15.
    Boss A, Bisdas S, Kolb A, Hofmann M, Ernemann U, Claussen CD, Pfannenberg C, Pichler BJ, Reimold M, Stegger L. Hybrid PET/MRI of intracranial masses: initial experiences and comparison to PET/CT. J Nucl Med. 2010;51(8):1198–205. Scholar
  16. 16.
    Thorwarth D, Müller AC, Pfannenberg C, Beyer T. Combined PET/MR imaging using (68)Ga-DOTATOC for radiotherapy treatment planning in meningioma patients. Recent Results Cancer Res. 2013;194:425–39.CrossRefPubMedGoogle Scholar
  17. 17.
    Haug AR, Auernhammer CJ, Wängler B, Schmidt GP, Uebleis C, Göke B, Cumming P, Bartenstein P, Tiling R, Hacker M. 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;51:1349–56.CrossRefPubMedGoogle Scholar
  18. 18.
    Kroiss A, Putzer D, Uprimny C, Decristoforo C, Gabriel M, Santner W, Kranewitter C, Warwitz B, Waitz D, Kendler D, Virgolini IJ. Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine. Eur J Nucl Med Mol Imaging. 2011;38:865–73.CrossRefPubMedGoogle Scholar
  19. 19.
    Kroiss A, Putzer D, Frech A, Decristoforo C, Uprimny C, Gasser RW, Shulkin BL, Url C, Widmann G, Prommegger R, Sprinzl GM, Fraedrich G, Virgolini IJ. A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma. Eur J Nucl Med Mol Imaging. 2013;40(12):1800–8. Scholar
  20. 20.
    Mittal BR, Agrawal K, Shukla J, Bhattacharya A, Singh B, Sood A, Bhansali A. Ga-68 DOTATATE PET/CT in neuroendocrine tumors: initial experience. J Postgrad Med Edu Res. 2013;47:1–6.CrossRefGoogle Scholar
  21. 21.
    Gupta SK, Singla S, Karunanithi S, Damle N, Bal C. Peptide receptor radionuclide therapy with (177)Lu DOTATATE in a case of recurrent carotid body paraganglioma with spinal metastases. Clin Nucl Med. 2014;39(5):440–1. Scholar
  22. 22.
    Puranik AD, Kulkarni HR, Singh A, Baum RP. Peptide receptor radionuclide therapy with (90)Y/ (177)Lu-labelled peptides for inoperable head and neck paragangliomas (glomus tumours). Eur J Nucl Med Mol Imaging. 2015;42(8):1223–30. Scholar
  23. 23.
    Vasamiliette J, Hohenberger P, Schoenberg S, Diehl S, Dinter DJ, Marx A, Stroebel P, Strauss LG, Dimitrakopoulou-Strauss A. Treatment monitoring with 18F-FDG PET in metastatic thymoma after 90Y-Dotatoc and selective internal radiation treatment (SIRT). Hell J Nucl Med. 2009;12:271–3.PubMedGoogle Scholar
  24. 24.
    Sollini M, Farioli D, Froio A, Chella A, Asti M, Boni R, Grassi E, Roncali M, Versari A, Erba PA. Brief report on the use of radiolabeled somatostatin analogs for the diagnosis and treatment of metastatic small-cell lung cancer patients. J Thorac Oncol. 2013;8:1095–101.CrossRefPubMedGoogle Scholar
  25. 25.
    Lapa C, Hänscheid H, Wild V, Pelzer T, Schirbel A, Werner RA, Droll S, Herrmann K, Buck AK, Lückerath K. Somatostatin receptor expression in small cell lung cancer as a prognostic marker and a target for peptide receptor radionuclide therapy. Oncotarget. 2016;7(15):20033–40. 10.18632/oncotarget.7706.PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Parghane RV, Talole S, Prabhash K, Basu S. Clinical response profile of metastatic/advanced pulmonary neuroendocrine tumors to peptide receptor radionuclide therapy with 177Lu-DOTATATE. Clin Nucl Med. 2017;42(6):428–35. Scholar
  27. 27.
    Gehler B, Paulsen F, Oksüz MO, Hauser TK, Eschmann SM, Bares R, Pfannenberg C, Bamberg M, Bartenstein P, Belka C, Ganswindt U. [68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning. Radiat Oncol. 2009;4:56.PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Heute D, Kostron H, von Guggenberg E, Ingorokva S, Gabriel M, Dobrozemsky G, Stockhammer G, Virgolini IJ. Response of recurrent high-grade glioma to treatment with (90)Y-DOTATOC. J Nucl Med. 2010;51:397–400.CrossRefPubMedGoogle Scholar
  29. 29.
    Nyuyki F, Plotkin M, Graf R, Michel R, Steffen I, Denecke T, Geworski L, Fahdt D, Brenner W, Wurm R. Potential impact of (68)Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas. Eur J Nucl Med Mol Imaging. 2010;37:310–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Gains JE, Bomanji JB, Fersht NL, Sullivan T, D’Souza D, Sullivan KP, Aldridge M, Waddington W, Gaze MN. 177Lu-DOTATATE molecular radiotherapy for childhood neuroblastoma. J Nucl Med. 2011;52:1041–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Waitz D, Putzer D, Kostron H, Virgolini IJ. Treatment of high-grade glioma with radiolabeled peptides. Methods. 2011;55:223–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Graf R, Plotkin M, Steffen IG, Wurm R, Wust P, Brenner W, Budach V, Badakhshi H. Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy--a case series. Head Face Med. 2012;8:1.PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Hänscheid H, Sweeney RA, Flentje M, Buck AK, Löhr M, Samnick S, Kreissl M, Verburg FA. PET SUV correlates with radionuclide uptake in peptide receptor therapy in meningioma. Eur J Nucl Med Mol Imaging. 2012;39:1284–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Graf R, Nyuyki F, Steffen IG, Michel R, Fahdt D, Wust P, Brenner W, Budach V, Wurm R, Plotkin M. Contribution of 68Ga-DOTATOC PET/CT to target volume delineation of skull base meningiomas treated with stereotactic radiation therapy. Int J Radiat Oncol Biol Phys. 2013;85(1):68–73. Scholar
  35. 35.
    Combs SE, Welzel T, Habermehl D, Rieken S, Dittmar JO, Kessel K, Jäkel O, Haberkorn U, Debus J. Prospective evaluation of early treatment outcome in patients with meningiomas treated with particle therapy based on target volume definition with MRI and 68Ga-DOTATOC-PET. Acta Oncol. 2013;52(3):514–20. Scholar
  36. 36.
    Golemi A, Ambrosini A, Cecchi P, Ruiu A, Chondrogiannis S, Farsad M, Rubello D. (68)Ga-DOTANOC PET/CT detection of multiple extracranial localizations in a patient with anaplastic meningioma. Rev Esp Med Nucl Imagen Mol. 2015;34(4):258–60. Scholar
  37. 37.
    Collamati F, Pepe A, Bellini F, Bocci V, Chiodi G, Cremonesi M, De Lucia E, Ferrari ME, Frallicciardi PM, Grana CM, Marafini M, Mattei I, Morganti S, Patera V, Piersanti L, Recchia L, Russomando A, Sarti A, Sciubba A, Senzacqua M, Solfaroli Camillocci E, Voena C, Pinci D, Faccini R. Toward radioguided surgery with β-decays: uptake of a somatostatin analogue, DOTATOC, in meningioma and high-grade glioma. J Nucl Med. 2015;56(1):3–8. Scholar
  38. 38.
    Madani I, Lomax AJ, Albertini F, Trnková P, Weber DC. Dose-painting intensity-modulated proton therapy for intermediate- and high-risk meningioma. Radiat Oncol. 2015;10:72. Scholar
  39. 39.
    Seystahl K, Stoecklein V, Schüller U, Rushing E, Nicolas G, Schäfer N, Ilhan H, Pangalu A, Weller M, Tonn JC, Sommerauer M, Albert NL. Somatostatin receptor-targeted radionuclide therapy for progressive meningioma: benefit linked to 68Ga-DOTATATE/−TOC uptake. Neuro-Oncology. 2016;18(11):1538–47.PubMedCentralPubMedGoogle Scholar
  40. 40.
    Gabriel M, Andergassen U, Putzer D, Kroiss A, Waitz D, Von Guggenberg E, Kendler D, Virgolini IJ. Individualized peptide-related-radionuclide-therapy concept using different radiolabelled somatostatin analogs in advanced cancer patients. Q J Nucl Med Mol Imaging. 2010;54:92–9.PubMedGoogle Scholar
  41. 41.
    Damle NA, Bal C, Gupta S, Singhal A. Discordance in 68Ga-DOTANOC and 177Lu-DOTATATE uptake in diagnostic and post-therapy scans in patients with medullary thyroid cancer-likely reasons. J Cancer Res Ther. 2013;9(4):754–5.CrossRefPubMedGoogle Scholar
  42. 42.
    Versari A, Sollini M, Frasoldati A, Fraternali A, Filice A, Froio A, Asti M, Fioroni F, Cremonini N, Putzer D, Erba PA. Differentiated thyroid cancer: a new perspective with radiolabeled somatostatin analogues for imaging and treatment of patients. Thyroid. 2014;24(4):715–26. Scholar
  43. 43.
    Traub-Weidinger T, Putzer D, von Guggenberg E, Dobrozemsky G, Nilica B, Kendler D, Bale R, Virgolini IJ. Multiparametric PET imaging in thyroid malignancy characterizing tumour heterogeneity: somatostatin receptors and glucose metabolism. Eur J Nucl Med Mol Imaging. 2015;42(13):1995–2001. Scholar
  44. 44.
    Basu S, Joshi A. 68Ga DOTATATE PET/CT in differentiated thyroid carcinoma with fibular metastasis and mixed response to sorafenib. Clin Nucl Med. 2016;41(10):772–3.CrossRefPubMedGoogle Scholar
  45. 45.
    Elboğa U, Özkaya M, Sayiner ZA, Çelen YZ. Lu-177 labelled peptide treatment for radioiodine refractory differentiated thyroid carcinoma. BMJ Case Rep. 2016;8:2016.Google Scholar
  46. 46.
    Salavati A, Prasad V, Schneider CP, Herbst R, Baum RP. Peptide receptor radionuclide therapy of Merkel cell carcinoma using (177)lutetium-labeled somatostatin analogs in combination with radiosensitizing chemotherapy: a potential novel treatment based on molecular pathology. Ann Nucl Med.2012;26(4):365–9. 1.Google Scholar
  47. 47.
    Schmidt MC, Uhrhan K, Markiefka B, et al. (68)Ga-DotaTATE PET-CT followed by Peptide Receptor Radiotherapy in combination with capecitabine in two patients with Merkel Cell Carcinoma. Int J Clin Exp Med. 2012;5(4):363–6.Google Scholar
  48. 48.
    Epstude M, Tornquist K, Riklin C, di Lenardo F, Winterhalder R, Hug U, Strobel K. Comparison of (18)F-FDG PET/CT and (68)Ga-DOTATATE PET/CT imaging in metastasized merkel cell carcinoma. Clin Nucl Med. 2013;38:283–4.Google Scholar
  49. 49.
    Chrisoulidou A, Kaltsas G, Ilias I, Grossman AB. The diagnosis and management of malignant phaeochromocytoma and paraganglioma. Endocr Relat Cancer. 2007;14:569–85.CrossRefPubMedGoogle Scholar
  50. 50.
    Safford SD, Coleman RE, Gockerman JP, Moore J, Feldman JM, Leight GS Jr, Tyler DS, Olson JA Jr. Iodine −131 metaiodobenzylguanidine is an effective treatment for malignant pheochromocytoma and paraganglioma. Surgery. 2003;134:956–62. discussion 962–953CrossRefPubMedGoogle Scholar
  51. 51.
    Kwekkeboom DJ, Teunissen JJ, Bakker WH, Kooij PP, de Herder WW, Feelders RA, van Eijck CH, Esser JP, Kam BL, Krenning EP. Radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol. 2005;23:2754–62.CrossRefPubMedGoogle Scholar
  52. 52.
    Van Essen M, Krenning EP, Kooij PP, Bakker WH, Feelders RA, de Herder WW, Wolbers JG, Kwekkeboom DJ. Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. J Nucl Med. 2006;47:1599–606.PubMedGoogle Scholar
  53. 53.
    Zovato S, Kumanova A, Demattè S, Sansovini M, Bodei L, Di Sarra D, Casagranda E, Severi S, Ambrosetti A, Schiavi F, Opocher G, Paganelli G. Peptide receptor radionuclide therapy (PRRT) with 177LuDOTATATE in individuals with neck or mediastinal paraganglioma (PGL). Horm Metab Res. 2012;44:411–4.CrossRefPubMedGoogle Scholar
  54. 54.
    Cecchin D, Schiavi F, Fanti S, Favero M, Manara R, Fassina A, Briani C, Allegri V, Sansovini M, Bui F, Paganelli G, Opocher G. Peptide receptor radionuclide therapy in a case of multiple spinal canal and cranial paragangliomas. J Clin Oncol. 2011;29:171–4.CrossRefGoogle Scholar
  55. 55.
    Makis W, McCann K, McEwan AJB. The challenges of treating paraganglioma patients with 177Lu-DOTATATE PRRT: catecholamine crises, tumor lysis syndrome and the need for modification of treatment protocols. Nucl Med Mol Imaging. 2015;49:223–30. Scholar
  56. 56.
    Lo Russo G, Pusceddu S, Prinzi N, Imbimbo M, Proto C, Signorelli D, Vitali M, Ganzinelli M, Maccauro M, Buzzoni R, Seregni E, de Braud F, Garassino MC. Peptide receptor radionuclide therapy: focus on bronchial neuroendocrine tumors. Tumor Biol. 2016;37:12991–3003. Scholar
  57. 57.
    Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol. 2001;12:941–5.CrossRefPubMedGoogle Scholar
  58. 58.
    Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, Haldemann A, Mueller-Brand J. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)YDOTATOC. J Nucl Med. 2002;43:610–6.PubMedGoogle Scholar
  59. 59.
    Bodei L, Cremonesi M, Zoboli S, Grana C, Bartolomei M, Rocca P, Caracciolo M, Mäcke HR, Chinol M, Paganelli G. Receptor mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study. Eur J Nucl Med Mol Imaging. 2003;30:207–16.CrossRefPubMedGoogle Scholar
  60. 60.
    Bodei L, Cremonesi M, Grana C, Rocca P, Bartolomei M, Chinol M, Paganelli G. Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2004;31:1038–46.CrossRefPubMedGoogle Scholar
  61. 61.
    Bodei L, Cremonesi M, Grana CM, Fazio N, Iodice S, Baio SM, Bartolomei M, Lombardo D, Ferrari ME, Sansovini M, Chinol M, Paganelli G. Peptide receptor radionuclide therapy with 177Lu-DOTATATE: the IEO phase I–II study. Eur J Nucl Med Mol Imaging. 2011;38:2125–35.CrossRefPubMedGoogle Scholar
  62. 62.
    Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, Mäcke HR, Rochlitz C, Müller-Brand J, Walter MA. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90YDOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol. 2011;29:2416–23.CrossRefPubMedGoogle Scholar
  63. 63.
    Van Essen M, Krenning EP, Bakker WH, de Herder WW, van Aken MO, Kwekkeboom DJ. Peptide receptor radionuclide therapy with 177Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin. Eur J Nucl Med Mol Imaging. 2007;34:1219–27.CrossRefPubMedGoogle Scholar
  64. 64.
    Ianniello A, Sansovini M, Severi S, Nicolini S, Grana CM, Massri K, Bongiovanni A, Antonuzzo L, Di Iorio V, Sarnelli A, Caroli P, Monti M, Scarpi E, Paganelli G. Peptide receptor radionuclide therapy with (177)Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and (18)F-FDG PET. Eur J Nucl Med Mol Imaging. 2016;43(6):1040–6.CrossRefPubMedGoogle Scholar
  65. 65.
    Khan S, Krenning EP, van Essen M, Kam BL, Teunissen JJ, Kwekkeboom DJ. Quality of life in 265 patients with gastroenteropancreatic or bronchial neuroendocrine tumors treated with [177Lu-DOTA0,Tyr3]octreotate. J Nucl Med. 2011;52:1361–8.CrossRefPubMedGoogle Scholar
  66. 66.
    Diakatou E, Alexandraki KI, Tsolakis AV, Kontogeorgos G, Chatzellis E, Leonti A, Kaltsas GA. Somatostatin and dopamine receptor expression in neuroendocrine neoplasms: correlation of immunohistochemical findings with somatostatin receptor scintigraphy visual scores. Clin Endocrinol. 2015;83(3):420–8.CrossRefGoogle Scholar
  67. 67.
    Cives M, Strosberg J. Radionuclide therapy for neuroendocrine tumors. Curr Oncol Rep. 2017;19:9. Scholar
  68. 68.
    Soga J, Yakuwa Y, Osaka M. Evaluation of 342 cases of mediastinal/thymic carcinoids collected from literature: a comparative study between typical carcinoids and atypical varieties. Ann Thorac Cardiovasc Surg. 1999;5:285–92.PubMedGoogle Scholar
  69. 69.
    Koukouraki S, Strauss LG, Georgoulias V, Eisenhut M, Haberkorn U, Dimitrakopoulou-Strauss A. Comparison of the pharmacokinetics of 68Ga-DOTATOC and [18F]FDG in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy. Eur J Nucl Med Mol Imaging. 2006;33(10):1115–22.CrossRefPubMedGoogle Scholar
  70. 70.
    Ambrosini V, Nanni C, Zompatori M, Campana D, Tomassetti P, Castellucci P, Allegri V, Rubello D, Montini G, Franchi R, Fanti S. 68Ga-DOTA-NOC PET/CT in comparison with CT for the detection of bone metastasis in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2010;37(4):722–7.CrossRefPubMedGoogle Scholar
  71. 71.
    Miederer M, Seidl S, Buck A, Scheidhauer K, Wester HJ, Schwaiger M, Perren A. Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in 68Ga-DOTATOC PET/CT. Eur J Nucl Med Mol Imaging. 2009;36(1):48–52.CrossRefPubMedGoogle Scholar
  72. 72.
    Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, Feelders RA, van Aken MO, Krenning EP. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26:2124–30.CrossRefPubMedGoogle Scholar
  73. 73.
    Teunissen JJ, Kwekkeboom DJ, Krenning EP. Quality of life in patients with gastroenteropancreatic tumors treated with [177Lu-DOTA0,Tyr3]octreotate. J Clin Oncol. 2004;22:2724–9.CrossRefPubMedGoogle Scholar
  74. 74.
    Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109.PubMedCentralCrossRefPubMedGoogle Scholar
  75. 75.
    Gerster-Gilliéron K, Forrer F, Maecke H, Mueller-Brand J, Merlo A, Cordier D. 90Y-DOTATOC as a therapeutic option for complex recurrent or progressive meningiomas. J Nucl Med. 2015;56(11):1748–51. Scholar
  76. 76.
    Goldsmith BJ, Wara WM, Wilson CB, Larson DA. Postoperative irradiation for subtotally resected meningiomas: a retrospective analysis of 140 patients treated from 1967 to 1990. J Neurosurg. 1994;80:195–2015.CrossRefPubMedGoogle Scholar
  77. 77.
    Nishio S, Morioka T, Inamura T, Takeshita I, Fukui M, Sasaki M, Nakamura K, Wakisaka S. Radiation-induced brain tumours: potential late complications of radiation therapy for brain tumours. Acta Neurochir. 1998;140:763–70.CrossRefPubMedGoogle Scholar
  78. 78.
    Milker-Zabel S, Zabel A, Schulz-Ertner D, Schlegel W, Wannenmacher M, Debus J. Fractionated stereotactic radiotherapy in patients with benign or atypica intracranial meningioma: long-term experience and prognostic factors. Int J Radiat Oncol Biol Phys. 2005;61:809–16.CrossRefPubMedGoogle Scholar
  79. 79.
    Reubi JC, Maurer R, Lamberts SW. Somatostatin binding sites in human leptomeninx. Neurosci Lett. 1986;70:183.CrossRefPubMedGoogle Scholar
  80. 80.
    Dutour A, Kumar U, Panetta R, Ouafik L, Fina F, Sasi R, Patel YC. Expression of somatostatin receptor subtypes in human brain tumors. Int J Cancer. 1998;76:620.CrossRefPubMedGoogle Scholar
  81. 81.
    Barresi V, Alafaci C, Salpietro F, Tuccari G. Sstr2A immunohistochemical expression in human meningiomas: is there a correlation with the histological grade, proliferation or microvessel density? Oncol Rep. 2008;20:485.PubMedGoogle Scholar
  82. 82.
    Sabet A, Ahmadzadehfar H, Herrlinger U, Wilinek W, Biersack HJ, Ezziddin S. Successful radiopeptide targeting of metastatic anaplastic meningioma: case report. Radiat Oncol. 2011;6:94.PubMedCentralCrossRefPubMedGoogle Scholar
  83. 83.
    Green S, Weiss GR. Southwest oncology group standard response criteria, endpoint definitions and toxicity criteria. Investig New Drugs. 1992;10:239.CrossRefGoogle Scholar
  84. 84.
    Bartolomei M, Bodei L, De Cicco C, Grana CM, Cremonesi M, Botteri E, Baio SM, Aricò D, Sansovini M, Paganelli G. Peptide receptor radionuclide therapy with 90Y_DOTATOC in recurrent meningioma. Eur J Nucl Med Mol Imaging. 2009;36:1407.CrossRefPubMedGoogle Scholar
  85. 85.
    Kreissl MC, Hänscheid H, Löhr M, Verburg FA, Schiller M, Lassmann M, Reiners C, Samnick SS, Buck AK, Flentje M, Sweeney RA. Combination of peptide receptor radionuclide therapy with fractionated external beam radiotherapy for treatment of advanced symptomatic meningioma. Radiat Oncol. 2012;7:99.PubMedCentralCrossRefPubMedGoogle Scholar
  86. 86.
    Minutoli F, Amato E, Sindoni A, Cardile D, Conti A, Herberg A, Baldari S. Peptide receptor radionuclide therapy in patients with inoperable meningiomas: our experience and review of the literature. Cancer Biother Radiopharm. 2014;29(5):193–9. Scholar
  87. 87.
    Eustatia-Rutten CF, Corssmit EP, Biermasz NR, Pereira AM, Romijn JA, Smit JW. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2006;91:313–9.CrossRefPubMedGoogle Scholar
  88. 88.
    Sherman SI. Thyroid carcinoma. Lancet. 2003;361:501–11.CrossRefPubMedGoogle Scholar
  89. 89.
    Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, Caillou B, Ricard M, Lumbroso JD, De Vathaire F, Schlumberger M. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: bene ts and limits of radio-iodine therapy. J Clin Endocrinol Metab. 2006;91:2892–9.CrossRefPubMedGoogle Scholar
  90. 90.
    Rouxel A, Hejblum G, Bernier MO, Boëlle PY, Ménégaux F, Mansour G, Hoang C, Aurengo A, Leenhardt L. Prognostic factors associated with the survival of patients developing loco-regional recurrences of differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2004;89(11):5362–8.CrossRefPubMedGoogle Scholar
  91. 91.
    Forssell-Aronsson EB, Nilsson O, Bejegard SA, Kolby L, Bernhardt P, Molne J, Hashemi SH, Wangberg B, Tisell LE, Ahlman H. 111InDTPA-D-Phe1-octreotide binding and somatostatin receptor subtypes in thyroid tumors. J Nucl Med. 2000;41:636–42.PubMedGoogle Scholar
  92. 92.
    Pisarek H, Stepien T, Kubiak R, Borkowska E, Pawlikowski M. Expression of somatostatin receptor subtypes in human thyroid tumors: the immunohistochemical and molecular biology (RT-PCR) investigation. Thyroid Res. 2009;2:1.PubMedCentralCrossRefPubMedGoogle Scholar
  93. 93.
    De Jong M, Bernard BF, De Bruin E, Van Gameren A, Bakker WH, Visser TJ, Ma ̈cke HR, Krenning EP. Internalization of radiolabeled [DTPA0]octreotide and [DOTA0,Tyr3]octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy. Nucl Med Commun. 1998;19:283–8.CrossRefPubMedGoogle Scholar
  94. 94.
    Eberle AN, Mild G. Receptor-mediated tumor targeting with radiopeptides. Part 1. General principles and methods. J Recept Signal Transduct Res. 2009;29:1–37.CrossRefPubMedGoogle Scholar
  95. 95.
    Waldherr C, Schumacher T, Pless M, Crazzolara A, Maecke HR, Nitzsche EU, Haldemann A, Mueller-Brand J. Radiopeptide transmitted internal irradiation of noniodophil thyroid cancer and conventionally untreatable medullary thyroid cancer using. Nucl Med Commun. 2001;22:673–8.CrossRefPubMedGoogle Scholar
  96. 96.
    Gorges R, Kahaly G, Müller-Brand J, Mäcke H, Roser HW, Bockisch A. Radionuclide-labeled somatostatin analogues for diagnostic and therapeutic purposes in nonmedullary thyroid cancer. Thyroid. 2011;11:647–59.CrossRefGoogle Scholar
  97. 97.
    Iten F, Muller B, Schindler C, Rasch H, Rochlitz C, Oertli D, Maecke HR, Muller-Brand J. Walter MA. [(90)YttriumDOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial. Cancer. 2009;115:2052–62.CrossRefPubMedGoogle Scholar
  98. 98.
    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.CrossRefPubMedGoogle Scholar
  99. 99.
    Baum RP, Kulkarni HR, Carreras C. Peptides and receptors in image-guided therapy: theranostics for neuroendocrine neoplasms. Semin Nucl Med. 2012;42:190–207.CrossRefPubMedGoogle Scholar
  100. 100.
    Baudin E, Schlumberger M. New therapeutic approaches for metastatic thyroid carcinoma. Lancet Oncol. 2007;8:148–56.CrossRefPubMedGoogle Scholar
  101. 101.
    Bertagna F, Giubbini R, Savelli G, Pizzocaro C, Rodella C, Biasiotto G, Lucchini S, Maroldi R, Rosenbaum J, Alavi A. A patient with medullary thyroid carcinoma and right ventricular cardiac metastasis treated by (90)Y-Dotatoc. Hell J Nucl Med. 2009;12:161–4.PubMedGoogle Scholar
  102. 102.
    Czepczyński R, Matysiak-Grześ M, Gryczyńska M, Bączyk M, Wyszomirska A, Stajgis M, Ruchała M. Peptide receptor radionuclide therapy of differentiated thyroid cancer: efficacy and toxicity. Arch Immunol Ther Exp. 2015;63(2):147–54.CrossRefGoogle Scholar
  103. 103.
    Iten F, Muller B, Schindler C, Rochlitz C, Oertli D, Macke HR, Muller-Brand J. Walter MA response to [90Yttrium-DOTA]-TOC treatment is associated with long-term survival benefit in metastasized medullary thyroid cancer: a phase II clinical trial. Clin Cancer Res. 2007;13(22 Pt 1):6696–702.CrossRefPubMedGoogle Scholar
  104. 104.
    Salavati A, Puranik A, Kulkarni HR, Budiawan H, Baum RP. Peptide receptor radionuclide therapy (PRRT) of medullary and nonmedullary thyroid cancer using radiolabeled somatostatin analogues. Semin Nucl Med. 2016;46(3):215–24.CrossRefPubMedGoogle Scholar
  105. 105.
    Basu S, Ranade R. Favorable response of metastatic merkel cell carcinoma to targeted 177Lu-DOTATATE therapy: will PRRT evolve to become an important approach in receptor-positive cases? J Nucl Med Technol. 2016;44(2):85–7. ReviewCrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Annibale Versari
    • 1
  • Angelina Filice
    • 1
  • Massimiliano Casali
    • 1
  • Martina Sollini
    • 2
  • Andrea Frasoldati
    • 3
  1. 1.Nuclear Medicine UnitArcispedale Santa Maria Nuova-IRCCSReggio EmiliaItaly
  2. 2.Department of Biomedical SciencesHumanitas UniversityMilanItaly
  3. 3.Endocrinology UnitArcispedale Santa Maria Nuova-IRCCSReggio EmiliaItaly

Personalised recommendations