Review article
Vol. 149 No. 0910 (2019)
Molecular imaging for neuroendocrine tumours: This article was corrected and republished online on April 3, 2019. Please see Erratum (Swiss Med Wkly. 2019;149:w20076)
- Kwadwo Antwi
- Guillaume Nicolas
- Damian Wild
- Emanuel Christ
-
Cite this as:
-
Swiss Med Wkly. 2019;149:w20017
-
Published
-
10.03.2019
Summary
Molecular imaging has found numerous applications in oncology as many tumours express or activate tumour specific target molecules or pathways. This relatively new imaging technique results in a better localisation of tumours and improved tumour staging, especially in the setting of hybrid imaging that is in combination with morphological imaging such as computed tomography. In well differentiated neuroendocrine tumours, somatostatin receptor imaging, as one of the first examples of receptor targeted imaging in humans, plays an important role in the diagnostic work-up of these patients. In poorly differentiated neuroendocrine tumours or medullary thyroid carcinoma, 18F-fluorodeoxyglucose PET/CT and dihydroxyphenylalanine PET/CT play an important role due to the limitations of the somatostatin receptor imaging in these tumour entities. These limitations prompted the development of innovations such as radiolabelled somatostatin receptor antagonists for imaging all types of NET and glucagon-like peptide-1 receptor agonists for the imaging of insulinomas. The current review summarises the actual state of knowledge in the field.
References
- 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. doi:.https://doi.org/10.1001/jamaoncol.2017.0589
- Reubi JC, Waser B. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging. 2003;30(5):781–93. doi:.https://doi.org/10.1007/s00259-003-1184-3
- Körner M. Specific biology of neuroendocrine tumors: Peptide receptors as molecular targets. Best Pract Res Clin Endocrinol Metab. 2016;30(1):19–31. doi:.https://doi.org/10.1016/j.beem.2016.01.001
- Deroose CM, Hindié E, Kebebew E, Goichot B, Pacak K, Taïeb D, et al. Molecular Imaging of Gastroenteropancreatic Neuroendocrine Tumors: Current Status and Future Directions. J Nucl Med. 2016;57(12):1949–56. doi:.https://doi.org/10.2967/jnumed.116.179234
- Öberg KE, Reubi JC, Kwekkeboom DJ, Krenning EP. Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy. Gastroenterology. 2010;139(3):742–53.e1. doi:.https://doi.org/10.1053/j.gastro.2010.07.002
- Rinke A, Müller H-H, Schade-Brittinger C, Klose KJ, Barth P, Wied M, et al.; PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009;27(28):4656–63. doi:.https://doi.org/10.1200/JCO.2009.22.8510
- Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, et al.; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371(3):224–33. doi:.https://doi.org/10.1056/NEJMoa1316158
- Susini C, Buscail L. Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol. 2006;17(12):1733–42. doi:.https://doi.org/10.1093/annonc/mdl105
- Woltering EA. Development of targeted somatostatin-based antiangiogenic therapy: a review and future perspectives. Cancer Biother Radiopharm. 2003;18(4):601–9. doi:.https://doi.org/10.1089/108497803322287691
- Feelders RA, de Herder WW, Neggers SJ, van der Lely AJ, Hofland LJ. Pasireotide, a multi-somatostatin receptor ligand with potential efficacy for treatment of pituitary and neuroendocrine tumors. Drugs Today (Barc). 2013;49(2):89–103. doi:.https://doi.org/10.1358/dot.2013.49.2.1915142
- de Jong M, Breeman WA, Bernard BF, Rolleman EJ, Hoflande LJ, Visser TJ, et al. Evaluation in vitro and in rats of 161Tb-DTPA-octreotide, a somatostatin analogue with potential for intraoperative scanning and radiotherapy. Eur J Nucl Med. 1995;22(7):608–16. doi:.https://doi.org/10.1007/BF01254561
- Körner M, Waser B, Schonbrunn A, Perren A, Reubi JC. Somatostatin receptor subtype 2A immunohistochemistry using a new monoclonal antibody selects tumors suitable for in vivo somatostatin receptor targeting. Am J Surg Pathol. 2012;36(2):242–52. doi:.https://doi.org/10.1097/PAS.0b013e31823d07f3
- 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. doi:.https://doi.org/10.2967/jnumed.106.035667
- Etchebehere EC, de Oliveira Santos A, Gumz B, Vicente A, Hoff PG, Corradi G, 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. doi:.https://doi.org/10.2967/jnumed.114.144543
- Pettinato C, Sarnelli A, Di Donna M, Civollani S, Nanni C, Montini G, et al. 68Ga-DOTANOC: biodistribution and dosimetry in patients affected by neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2008;35(1):72–9. doi:.https://doi.org/10.1007/s00259-007-0587-y
- Delle Fave G, Kwekkeboom DJ, Van Cutsem E, Rindi G, Kos-Kudla B, Knigge U, et al.; Barcelona Consensus Conference participants. ENETS Consensus Guidelines for the management of patients with gastroduodenal neoplasms. Neuroendocrinology. 2012;95(2):74–87. doi:.https://doi.org/10.1159/000335595
- Garin E, Le Jeune F, Devillers A, Cuggia M, de Lajarte-Thirouard AS, Bouriel C, et al. Predictive value of 18F-FDG PET and somatostatin receptor scintigraphy in patients with metastatic endocrine tumors. J Nucl Med. 2009;50(6):858–64. doi:.https://doi.org/10.2967/jnumed.108.057505
- Koopmans KP, Neels OC, Kema IP, Elsinga PH, Sluiter WJ, Vanghillewe K, et al. Improved staging of patients with carcinoid and islet cell tumors with 18F-dihydroxy-phenyl-alanine and 11C-5-hydroxy-tryptophan positron emission tomography. J Clin Oncol. 2008;26(9):1489–95. doi:.https://doi.org/10.1200/JCO.2007.15.1126
- Ambrosini V, Tomassetti P, Castellucci P, Campana D, Montini G, Rubello D, et al. Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours. Eur J Nucl Med Mol Imaging. 2008;35(8):1431–8. doi:.https://doi.org/10.1007/s00259-008-0769-2
- Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al.; NETTER-1 Trial Investigators. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 2017;376(2):125–35. doi:.https://doi.org/10.1056/NEJMoa1607427
- Brubaker PL, Drucker DJ. Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors. Receptors Channels. 2002;8(3-4):179–88. doi:.https://doi.org/10.3109/10606820213687
- Burcelin R, Da Costa A, Drucker D, Thorens B. Glucose competence of the hepatoportal vein sensor requires the presence of an activated glucagon-like peptide-1 receptor. Diabetes. 2001;50(8):1720–8. doi:.https://doi.org/10.2337/diabetes.50.8.1720
- Farilla L, Bulotta A, Hirshberg B, Li Calzi S, Khoury N, Noushmehr H, et al. Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology. 2003;144(12):5149–58. doi:.https://doi.org/10.1210/en.2003-0323
- Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131–57. doi:.https://doi.org/10.1053/j.gastro.2007.03.054
- Nauck MA. Unraveling the science of incretin biology. Eur J Intern Med. 2009;20(Suppl 2):S303–8. doi:.https://doi.org/10.1016/j.ejim.2009.05.012
- Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem. 1992;267(11):7402–5.
- Grant CS. Insulinoma. Best Pract Res Clin Gastroenterol. 2005;19(5):783–98. doi:.https://doi.org/10.1016/j.bpg.2005.05.008
- Grant CS. Insulinoma. Best Pract Res Clin Gastroenterol. 2005;19(5):783–98. doi:.https://doi.org/10.1016/j.bpg.2005.05.008
- Hackert T, Hinz U, Fritz S, Strobel O, Schneider L, Hartwig W, et al. Enucleation in pancreatic surgery: indications, technique, and outcome compared to standard pancreatic resections. Langenbecks Arch Surg. 2011;396(8):1197–203. doi:.https://doi.org/10.1007/s00423-011-0801-z
- Wenning AS, Kirchner P, Antwi K, Fani M, Wild D, Christ E, et al. Preoperative Glucagon-like peptide-1 receptor imaging reduces surgical trauma and pancreatic tissue loss in insulinoma patients: a report of three cases. Patient Saf Surg. 2015;9(1):23. doi:.https://doi.org/10.1186/s13037-015-0064-7
- Liu H, Peng C, Zhang S, Wu Y, Fang H, Sheng H, et al. Strategy for the surgical management of insulinomas: analysis of 52 cases. Dig Surg. 2007;24(6):463–70. doi:.https://doi.org/10.1159/000111822
- Reubi JC, Waser B. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging. 2003;30(5):781–93. doi:.https://doi.org/10.1007/s00259-003-1184-3
- Reubi JC, Körner M, Waser B, Mazzucchelli L, Guillou L. High expression of peptide receptors as a novel target in gastrointestinal stromal tumours. Eur J Nucl Med Mol Imaging. 2004;31(6):803–10. doi:.https://doi.org/10.1007/s00259-004-1476-2
- Wild D, Mäcke H, Christ E, Gloor B, Reubi JC. Glucagon-like peptide 1-receptor scans to localize occult insulinomas. N Engl J Med. 2008;359(7):766–8. doi:.https://doi.org/10.1056/NEJMc0802045
- Christ E, Wild D, Forrer F, Brändle M, Sahli R, Clerici T, et al. Glucagon-like peptide-1 receptor imaging for localization of insulinomas. J Clin Endocrinol Metab. 2009;94(11):4398–405. doi:.https://doi.org/10.1210/jc.2009-1082
- Antwi K, Fani M, Nicolas G, Rottenburger C, Heye T, Reubi JC, et al. Localization of Hidden Insulinomas with 68Ga-DOTA-Exendin-4 PET/CT: A Pilot Study. J Nucl Med. 2015;56(7):1075–8. doi:.https://doi.org/10.2967/jnumed.115.157768
- Antwi K, Fani M, Heye T, Nicolas G, Rottenburger C, Kaul F, et al. Comparison of glucagon-like peptide-1 receptor (GLP-1R) PET/CT, SPECT/CT and 3T MRI for the localisation of occult insulinomas: evaluation of diagnostic accuracy in a prospective crossover imaging study. Eur J Nucl Med Mol Imaging. 2018;45(13):2318–27. doi:.https://doi.org/10.1007/s00259-018-4101-5
- Ginj M, Zhang H, Waser B, Cescato R, Wild D, Wang X, et al. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proc Natl Acad Sci USA. 2006;103(44):16436–41. doi:.https://doi.org/10.1073/pnas.0607761103
- Wadas TJ, Eiblmaier M, Zheleznyak A, Sherman CD, Ferdani R, Liang K, et al. Preparation and biological evaluation of 64Cu-CB-TE2A-sst2-ANT, a somatostatin antagonist for PET imaging of somatostatin receptor-positive tumors. J Nucl Med. 2008;49(11):1819–27. doi:.https://doi.org/10.2967/jnumed.108.054502
- Cescato R, Waser B, Fani M, Reubi JC. Evaluation of 177Lu-DOTA-sst2 antagonist versus 177Lu-DOTA-sst2 agonist binding in human cancers in vitro. J Nucl Med. 2011;52(12):1886–90. doi:.https://doi.org/10.2967/jnumed.111.095778
- Wild D, Fani M, Behe M, Brink I, Rivier JE, Reubi JC, et al. First clinical evidence that imaging with somatostatin receptor antagonists is feasible. J Nucl Med. 2011;52(9):1412–7. doi:.https://doi.org/10.2967/jnumed.111.088922
- Cescato R, Erchegyi J, Waser B, Piccand V, Maecke HR, Rivier JE, et al. Design and in vitro characterization of highly sst2-selective somatostatin antagonists suitable for radiotargeting. J Med Chem. 2008;51(13):4030–7. doi:.https://doi.org/10.1021/jm701618q
- Nicolas GP, Beykan S, Bouterfa H, Kaufmann J, Bauman A, Lassmann M, et al. Safety, Biodistribution, and Radiation Dosimetry of 68Ga-OPS202 in Patients with Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Phase I Imaging Study. J Nucl Med. 2018;59(6):909–14. doi:.https://doi.org/10.2967/jnumed.117.199737
- Vera P, Thureau S, Chaumet-Riffaud P, Modzelewski R, Bohn P, Vermandel M, et al. Phase II Study of a Radiotherapy Total Dose Increase in Hypoxic Lesions Identified by 18F-Misonidazole PET/CT in Patients with Non-Small Cell Lung Carcinoma (RTEP5 Study). J Nucl Med. 2017;58(7):1045–53. doi:.https://doi.org/10.2967/jnumed.116.188367
- Wild D, Fani M, Fischer R, Del Pozzo L, Kaul F, Krebs S, et al. Comparison of somatostatin receptor agonist and antagonist for peptide receptor radionuclide therapy: a pilot study. J Nucl Med. 2014;55(8):1248–52. doi:.https://doi.org/10.2967/jnumed.114.138834
- Nicolas GP, Mansi R, McDougall L, Kaufmann J, Bouterfa H, Wild D, et al. Biodistribution, Pharmacokinetics, and Dosimetry of 177Lu-, 90Y-, and 111In-Labeled Somatostatin Receptor Antagonist OPS201 in Comparison to the Agonist 177Lu-DOTATATE: The Mass Effect. J Nucl Med. 2017;58(9):1435–41. doi:.https://doi.org/10.2967/jnumed.117.191684
- Wells SA, Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, et al.; American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610. doi:.https://doi.org/10.1089/thy.2014.0335
- Rottenburger C, Nicolas G, McDougall L, Kaul F, Christ E, Schibli R, et al. Imaging of Advanced Medullary Thyroid Carcinoma with the CCK-2 Receptor Agonist 177Lu-PP-F11N – Preliminary Proof of the Principle within the “Lumed” Study. 15th Annu Eur Neuroendocr Tumor Soc Conf. 2018.
- Körner M, Waser B, Reubi JC. Does somatostatin or gastric inhibitory peptide receptor expression correlate with tumor grade and stage in gut neuroendocrine tumors? Neuroendocrinology. 2015;101(1):45–57. doi:.https://doi.org/10.1159/000371804
- Gourni E, Waser B, Clerc P, Fourmy D, Reubi JC, Maecke HR. The glucose-dependent insulinotropic polypeptide receptor: a novel target for neuroendocrine tumor imaging—first preclinical studies. J Nucl Med. 2014;55(6):976–82. doi:.https://doi.org/10.2967/jnumed.113.133744