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Somatostatin Receptor Positron Emission Tomography: Beyond Gastroenteropancreatic Neuroendocrine Tumors

  • Nuclear Medicine & PET/CT Imaging (R Flavell, Section Editor)
  • Published:
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Abstract

Purpose of Review

Similar to various gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), somatostatin receptors (SSTRs) are overexpressed in a wide array of malignant and benign conditions. Using somatostatin positron emission tomography (PET) analogs ([68Ga]DOTA-peptides) this overexpression of SSTRs can be exploited for clinical management in terms of diagnosis, therapy, and for peptide receptor radionuclide therapy (PRRT).

Recent Findings

Recent reports suggest that [68Ga]DOTA-peptide PET tracers have an emerging role in the management of wide array of non-GEP-NETs due to overexpression of SSTRs. The potential role of SSTR-PET imaging in the management of medullary thyroid cancer, paraganglioma, Merkel cell carcinoma, phosphaturic mesenchymal tumors, and inflammation will be discussed. The emerging role of theranostic and personalized medicine with PRRT using peptides labeled with yttrium-90 (90Y) or lutetium-177 (177Lu) beta emitters will also be discussed.

Summary

SSTR-PET imaging with [68Ga]DOTA-peptides has utility in malignant and benign conditions other than GEP-NETs. Combining SSTR-PET with other anatomic and functional imaging modalities has demonstrated superior diagnostic accuracy. The presence of SSTRs in these conditions opens up new possibilities in the management of these conditions in terms of imaging and therapeutics.

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References

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  1. Reichlin S. Somatostatin. N Engl J Med. 1983;309(24):1495–501.

    Article  CAS  Google Scholar 

  2. Hofman MS, Lau WF, Hicks RJ. Somatostatin receptor imaging with 68 Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics. 2015;35(2):500–16.

    Article  Google Scholar 

  3. ••Sanli Y, Garg I, Kandathil A, Kendi T, Zanetti MJB, Kuyumcu S, Subramaniam RM. Neuroendocrine tumor diagnosis and management: (68)Ga-DOTATATE PET/CT. AJR Am J Roentgenol. 2018;211(2):267–77. This is a nice review article on DOTATATE PET imaging of well-differentiated neuroendocrine tumors and discusses its potential complementary role when used in tandem with FDG PET/CT in moderately and poorly differentiated neuroendocrine tumors.

  4. ••Hope TA, Bergsland EK, Bozkurt MF, Graham M, Heaney AP, Herrmann K, Howe JR, Kulke MH, Kunz PL, Mailman J et al. Appropriate use criteria for somatostatin receptor PET imaging in neuroendocrine tumors. J Nucl Med. 2018;59(1):66–74. This manuscript provides the appropriate use criteria for somatostatin receptor PET imaging of neuroendocrine tumors. The manuscript also covers several technical aspects of somatostatin receptor PET imaging.

    Article  Google Scholar 

  5. Bombardieri E, Ambrosini V, Aktolun C, Baum RP, Bishof-Delaloye A, Del Vecchio S, Maffioli L, Mortelmans L, Oyen W, Pepe G, et al. 111In-pentetreotide scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging. 2010;37(7):1441–8.

    Article  Google Scholar 

  6. Agool A, Slart R, Dierckx R, Kluin PM, Visser L, Jager PL, Vellenga E. Somatostatin receptor scintigraphy might be useful for detecting skeleton abnormalities in patients with multiple myeloma and plasmacytoma. Eur J Nucl Med Mol Imaging. 2010;37:124–30.

    Article  CAS  Google Scholar 

  7. Sharma P, Singh H, Bal C, Kumar R. PET/CT imaging of neuroendocrine tumors with (68)Gallium-labeled somatostatin analogues: an overview and single institutional experience from India. Indian J Nucl Med. 2014;29(1):2–12.

    Article  Google Scholar 

  8. Dalm VA, van Hagen PM, van Koetsveld PM, Achilefu S, Houtsmuller AB, Pols DH, van der Lely AJ, Lamberts SW, Hofland LJ. Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells. Am J Physiol Endocrinol Metab. 2003;285(2):E344–53.

    Article  CAS  Google Scholar 

  9. Wu C, Li F, Niu G, Chen X. PET imaging of inflammation biomarkers. Theranostics. 2013;3(7):448–66.

    Article  Google Scholar 

  10. Nicolas GP, Schreiter N, Kaul F, Uiters J, Bouterfa H, Kaufmann J, Erlanger TE, Cathomas R, Christ E, Fani M, et al. Sensitivity comparison of (68)Ga-OPS202 and (68)Ga-DOTATOC PET/CT in patients with gastroenteropancreatic neuroendocrine tumors: a prospective phase II imaging study. J Nucl Med. 2018;59(6):915–21.

    Article  CAS  Google Scholar 

  11. Kulkarni HR, Baum RP. Theranostics with Ga-68 somatostatin receptor PET/CT: monitoring response to peptide receptor radionuclide therapy. PET Clin. 2014;9(1):91–7.

    Article  Google Scholar 

  12. 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.

    Article  Google Scholar 

  13. Virgolini I, Ambrosini V, Bomanji JB, Baum RP, Fanti S, Gabriel M, Papathanasiou ND, Pepe G, Oyen W, De Cristoforo C, 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.

    Article  Google Scholar 

  14. Intenzo CM, Jabbour S, Lin HC, Miller JL, Kim SM, Capuzzi DM, Mitchell EP. Scintigraphic imaging of body neuroendocrine tumors. Radiographics. 2007;27(5):1355–69.

    Article  Google Scholar 

  15. Tran K, Khan S, Taghizadehasl M, Palazzo F, Frilling A, Todd JF, Al-Nahhas A. Gallium-68 Dotatate PET/CT is superior to other imaging modalities in the detection of medullary carcinoma of the thyroid in the presence of high serum calcitonin. Hell J Nucl Med. 2015;18(1):19–24.

    PubMed  Google Scholar 

  16. Priya SR, Dravid CS, Digumarti R, Dandekar M. Targeted therapy for medullary thyroid cancer: a review. Front Oncol. 2017;7:238.

    Article  CAS  Google Scholar 

  17. Yamaga LYI, Cunha ML, Campos Neto GC, Garcia MRT, Yang JH, Camacho CP, Wagner J, Funari MBG. (68)Ga-DOTATATE PET/CT in recurrent medullary thyroid carcinoma: a lesion-by-lesion comparison with (111)In-octreotide SPECT/CT and conventional imaging. Eur J Nucl Med Mol Imaging. 2017;44(10):1695–701.

    Article  CAS  Google Scholar 

  18. Naswa N, Sharma P, Suman Kc S, Lata S, Kumar R, Malhotra A, Bal C. Prospective evaluation of 68 Ga-DOTA-NOC PET-CT in patients with recurrent medullary thyroid carcinoma: comparison with 18F-FDG PET-CT. Nucl Med Commun. 2012;33(7):766–74.

    Article  Google Scholar 

  19. Conry BG, Papathanasiou ND, Prakash V, Kayani I, Caplin M, Mahmood S, Bomanji JB. Comparison of (68)Ga-DOTATATE and (18)F-fluorodeoxyglucose PET/CT in the detection of recurrent medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2010;37(1):49–57.

    Article  CAS  Google Scholar 

  20. Slavikova K, Montravers F, Treglia G, Kunikowska J, Kaliska L, Vereb M, Talbot JN, Balogova S. What is currently the best radiopharmaceutical for the hybrid PET/CT detection of recurrent medullary thyroid carcinoma? Curr Radiopharm. 2013;6(2):96–105.

    Article  CAS  Google Scholar 

  21. Treglia G, Castaldi P, Villani MF, Perotti G, de Waure C, Filice A, Ambrosini V, Cremonini N, Santimaria M, Versari A, et al. Comparison of 18F-DOPA, 18F-FDG and 68 Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2012;39(4):569–80.

    Article  CAS  Google Scholar 

  22. 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.

    Article  CAS  Google Scholar 

  23. Vaisman F, Rosado de Castro PH, Lopes FP, Kendler DB, Pessoa CH, Bulzico DA, de Carvalho LD, Vilhena B, Vaisman M, Carneiro M, et al. Is there a role for peptide receptor radionuclide therapy in medullary thyroid cancer? Clin Nucl Med. 2015;40(2):123–7.

    Article  Google Scholar 

  24. Bodei L, Handkiewicz-Junak D, Grana C, Mazzetta C, Rocca P, Bartolomei M, Lopera Sierra M, Cremonesi M, Chinol M, Macke HR, et al. Receptor radionuclide therapy with 90Y-DOTATOC in patients with medullary thyroid carcinomas. Cancer Biother Radiopharm. 2004;19(1):65–71.

    Article  CAS  Google Scholar 

  25. Ellison DA, Parham DM. Tumors of the autonomic nervous system. Am J Clin Pathol. 2001;115:S46–55.

    PubMed  Google Scholar 

  26. Carrasquillo JA, Chen CC. Molecular imaging of neuroendocrine tumors. Semin Oncol. 2010;37(6):662–79.

    Article  CAS  Google Scholar 

  27. Taieb D, Timmers HJ, Hindie E, Guillet BA, Neumann HP, Walz MK, Opocher G, de Herder WW, Boedeker CC, de Krijger RR, et al. EANM 2012 guidelines for radionuclide imaging of phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging. 2012;39(12):1977–95.

    Article  CAS  Google Scholar 

  28. Rufini V, Treglia G, Castaldi P, Perotti G, Giordano A. Comparison of metaiodobenzylguanidine scintigraphy with positron emission tomography in the diagnostic work-up of pheochromocytoma and paraganglioma: a systematic review. Quart J Nucl Med Mol Imaging. 2013;57(2):122–33.

    CAS  Google Scholar 

  29. Naji M. A AL-N: (6)(8)Ga-labelled peptides in the management of neuroectodermal tumours. Eur J Nucl Med Mol Imaging. 2012;39(1):S61–7.

    Article  Google Scholar 

  30. Tan TH, Hussein Z, Saad FF, Shuaib IL. Diagnostic performance of (68)Ga-DOTATATE PET/CT, (18)F-FDG PET/CT and (131)I-MIBG scintigraphy in mapping metastatic pheochromocytoma and paraganglioma. Nucl Med Mol Imaging. 2015;49(2):143–51.

    Article  CAS  Google Scholar 

  31. Chang CA, Pattison DA, Tothill RW, Kong G, Akhurst TJ, Hicks RJ, Hofman MS. (68)Ga-DOTATATE and (18)F-FDG PET/CT in Paraganglioma and pheochromocytoma: utility, patterns and heterogeneity. Cancer Imaging. 2016;16(1):22.

    Article  Google Scholar 

  32. ••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. 2014:194123. The manuscript is an earlier review of SSTR PET imaging used in tumors other than gastroenteropancreatic neuroendocrine tumors.

  33. Jha A, Ling A, Millo C, Gupta G, Viana B, Lin FI, Herscovitch P, Adams KT, Taieb D, Metwalli AR, et al. Superiority of (68)Ga-DOTATATE over (18)F-FDG and anatomic imaging in the detection of succinate dehydrogenase mutation (SDHx)-related pheochromocytoma and paraganglioma in the pediatric population. Eur J Nucl Med Mol Imaging. 2018;45(5):787–97.

    Article  CAS  Google Scholar 

  34. Archier A, Varoquaux A, Garrigue P, Montava M, Guerin C, Gabriel S, Beschmout E, Morange I, Fakhry N, Castinetti F, et al. Prospective comparison of (68)Ga-DOTATATE and (18)F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases. Eur J Nucl Med Mol Imaging. 2016;43(7):1248–57.

    Article  CAS  Google Scholar 

  35. Kwekkeboom DJ, Hoff AM, Lamberts SW, Oei HY, Krenning EP. Somatostatin analogue scintigraphy. A simple and sensitive method for the in vivo visualization of Merkel cell tumors and their metastases. Arch Dermatol. 1992;128(6):818–21.

    Article  CAS  Google Scholar 

  36. Hawryluk EB, O’Regan KN, Sheehy N, Guo Y, Dorosario A, Sakellis CG, Jacene HA, Wang LC. Positron emission tomography/computed tomography imaging in Merkel cell carcinoma: a study of 270 scans in 97 patients at the Dana-Farber/Brigham and Women’s Cancer Center. J Am Acad Dermatol. 2013;68(4):592–9.

    Article  Google Scholar 

  37. Siva S, Byrne K, Seel M, Bressel M, Jacobs D, Callahan J, Laing J, Macmanus MP, Hicks RJ. 18F-FDG PET provides high-impact and powerful prognostic stratification in the staging of Merkel cell carcinoma: a 15-year institutional experience. J Nucl Med. 2013;54(8):1223–9.

    Article  CAS  Google Scholar 

  38. Buder K, Lapa C, Kreissl MC, Schirbel A, Herrmann K, Schnack A, Brocker EB, Goebeler M, Buck AK, Becker JC. Somatostatin receptor expression in Merkel cell carcinoma as target for molecular imaging. BMC Cancer. 2014;14:268.

    Article  Google Scholar 

  39. 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(4):283–4.

    Article  Google Scholar 

  40. 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.

    Article  Google Scholar 

  41. Schmidt MC, Uhrhan K, Markiefka B, Hasselbring L, Schlaak M, Cremer B, Kunze S, Baum RP, Dietlein M. (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.

    PubMed  PubMed Central  Google Scholar 

  42. Meier G, Waldherr C, Herrmann R, Maecke H, Mueller-Brand J, Pless M. Successful targeted radiotherapy with 90Y-DOTATOC in a patient with Merkel cell carcinoma. Case Rep Oncol. 2004;66(2):160–3.

    CAS  Google Scholar 

  43. Mathis DA, Stehel EJ Jr, Beshay JE, Mickey BE, Folpe AL, Raisanen J. Intracranial phosphaturic mesenchymal tumors: report of 2 cases. J Neurosurg. 2013;118(4):903–7.

    Article  Google Scholar 

  44. Houang M, Clarkson A, Sioson L, Elston MS, Clifton-Bligh RJ, Dray M, Ranchere-Vince D, Decouvelaere AV, de la Fouchardiere A, Gill AJ. Phosphaturic mesenchymal tumors show positive staining for somatostatin receptor 2A (SSTR2A). Hum Pathol. 2013;44(12):2711–8.

    Article  CAS  Google Scholar 

  45. Clifton-Bligh RJ, Hofman MS, Duncan E, Sim Ie W, Darnell D, Clarkson A, Wong T, Walsh JP, Gill AJ, Ebeling PR, et al. Improving diagnosis of tumor-induced osteomalacia with Gallium-68 DOTATATE PET/CT. J Clin Endocrinol Metab. 2013;98(2):687–94.

    Article  CAS  Google Scholar 

  46. •El-Maouche D, Sadowski SM, Papadakis GZ, Guthrie L, Cottle-Delisle C, Merkel R, Millo C, Chen CC, Kebebew E, Collins MT: (68)Ga-DOTATATE for tumor localization in tumor-induced osteomalacia. J Clin Endocrinol Metab. 2016;101(10):3575–81. The manuscript is one of the largest studies of the use of DOTATATE PET for detection of phosphaturic mesenchymal tumors in patients with tumor-induced osteomalacia.

    Article  CAS  Google Scholar 

  47. Basu S, Fargose P. 177Lu-DOTATATE PRRT in recurrent skull-base phosphaturic mesenchymal tumor causing osteomalacia: a potential application of PRRT beyond neuroendocrine tumors. J Nucl Med Technol. 2016;44(4):248–50.

    Article  Google Scholar 

  48. Chareonthaitawee P, Beanlands RS, Chen W, Dorbala S, Miller EJ, Murthy VL, Birnie DH, Chen ES, Cooper LT, Tung RH, et al. Joint SNMMI-ASNC expert consensus document on the role of (18)F-FDG PET/CT in cardiac sarcoid detection and therapy monitoring. J Nucl Med. 2017;58(8):1341–53.

    Article  CAS  Google Scholar 

  49. Dorbala S, Di Carli MF, Delbeke D, Abbara S, DePuey EG, Dilsizian V, Forrester J, Janowitz W, Kaufmann PA, Mahmarian J, et al. SNMMI/ASNC/SCCT guideline for cardiac SPECT/CT and PET/CT 1.0. J Nucl Med. 2013;54(8):1485–507.

    Article  Google Scholar 

  50. Li X, Bauer W, Kreissl MC, Weirather J, Bauer E, Israel I, Richter D, Riehl G, Buck A, Samnick S. Specific somatostatin receptor II expression in arterial plaque: (68)Ga-DOTATATE autoradiographic, immunohistochemical and flow cytometric studies in apoE-deficient mice. Atherosclerosis. 2013;230(1):33–9.

    Article  CAS  Google Scholar 

  51. Li X, Samnick S, Lapa C, Israel I, Buck AK, Kreissl MC, Bauer W. 68 Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with18F-FDG, calcium burden and risk factors. EJNMMI Res. 2012;2(1):52.

    Article  Google Scholar 

  52. Tarkin JM, Joshi FR, Evans NR, Chowdhury MM, Figg NL, Shah AV, Starks LT, Martin-Garrido A, Manavaki R, Yu E, et al. Detection of Atherosclerotic Inflammation by (68)Ga-DOTATATE PET Compared to [(18)F]FDG PET Imaging. J Am Coll Cardiol. 2017;69(14):1774–91.

    Article  CAS  Google Scholar 

  53. Gormsen LC, Haraldsen A, Kramer S, Dias AH, Kim WY, Borghammer P. A dual tracer (68)Ga-DOTANOC PET/CT and (18)F-FDG PET/CT pilot study for detection of cardiac sarcoidosis. EJNMMI Res. 2016;6(1):52.

    Article  Google Scholar 

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Authors and Affiliations

  1. Division of Molecular Imaging & Therapeutics and Neuroradiology, Department of Radiology, University of Alabama at Birmingham, 619 19th Street South, Birmingham, AL, 35249-6835, USA

    Gagandeep Choudhary

  2. Division of Abdominal Imaging and Molecular Imaging & Therapeutics, Department of Radiology, University of Alabama at Birmingham, JTN 325, Birmingham, AL, 35249, USA

    Samuel Galgano

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Choudhary, G., Galgano, S. Somatostatin Receptor Positron Emission Tomography: Beyond Gastroenteropancreatic Neuroendocrine Tumors. Curr Radiol Rep 7, 15 (2019). https://doi.org/10.1007/s40134-019-0322-z

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