Neuroendokrine Tumoren – von der morphologischen zur funktionellen Bildgebung

Im Rahmen der Primärabklärung von neuroendokrinen Tumoren (NET) kommen neben der Ultraschalldiagnostik die Computertomografie und die Magnetresonanztomografie zum Einsatz. Je nach Verfügbarkeit stellt darüber hinaus die funktionelle Bildgebung mittels Szintigrafie bzw. Single-Photon-Emissionscomputertomografie (SPECT) und Positronenemissionstomografie (PET) eine obligate Untersuchungsmethode für die Abklärung von NET dar.

Kernaussagen

• Neuroendokrine Tumoren sind eine relativ seltene Tumorentität, die jedoch eine stetig steigende Inzidenz aufweisen. Dieser Anstieg ist überwiegend auf die moderne Bildgebung zurückzuführen, die eine Diagnostik neuroendokriner Tumoren auch in früheren Stadien ermöglich.

• Die Ultraschalldiagnostik stellt bei neuroendokrinen Tumoren eher eine Untersuchungsmodalität zur gezielten Diagnostik bestimmter Regionen dar (z. B. Endosonografie, Lebersonografie).

• Die CT- und MRT-Bildgebung zeigen eine ähnliche Sensitivität und Spezifität im Rahmen der Primärdiagnostik und sollten nach Möglichkeit immer unter Verwendung von Kontrastmittel durchgeführt werden. Die MRT-Bildgebung eignet sich insbesondere zur Abklärung hepatischer Metastasen, bei der zusätzlich zur Kontrastmittelgabe die Beurteilung diffusionsgewichteter Sequenzen von großer Bedeutung ist.

• Ein besonderes Merkmal neuroendokriner Tumoren ist die (Über-)Expression von Somatostatin-Rezeptoren auf der Zelloberfläche, welche die Grundlage für die nuklearmedizinische Bildgebung und Therapie darstellt. Die Rezeptoren dienen mittels diagnostischen und therapeutischen Radionukliden markierten Somatostatin-Analoga als Zielstruktur.

• Den Referenzstandard für die funktionelle Bildgebung gastroenteropankreatischer neuroendokriner Tumoren stellt die PET-Bildgebung mit überwiegend ⁶⁸Ga-markierten Somatostatin-Analoga dar. Neuere Entwicklungen beinhalten dabei auch mittels ⁶⁴Cu oder ¹⁸F markierte Somatostatin-Analoga, die im Vergleich zum Generatorprodukt ⁶⁸Ga pharmakokinetische Vorteile aufweisen.

• Darüber hinaus können auch andere Radiopharmaka wie beispielsweise ¹⁸F-FDG, ¹⁸F-DOPA oder ¹²³I/¹³¹I-MIBG für die Bildgebung und das Therapiemanagement neuroendokriner Tumoren von großer Bedeutung sein. Diese werden in diesem Beitrag jedoch nicht im Detail beleuchtet.

Schlüsselwörter

NET - Bildgebung - CT - MRT - PET/CT - Somatostatin-Analoga

Publication History

Article published online:
11 March 2022

• Literatur

• 1 Man D, Wu J, Shen Z. et al. Prognosis of patients with neuroendocrine tumor: a SEER database analysis. Cancer Manag Res 2018; 10: 5629-5638 DOI: 10.2147/CMAR.S174907. (PMID: 30519109)
• 2 Dasari A, Shen C, Halperin D. et al. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol 2017; 3: 1335-1342 DOI: 10.1001/jamaoncol.2017.0589. (PMID: 28448665)
• 3 Scherubl H, Streller B, Stabenow R. et al. Clinically detected gastroenteropancreatic neuroendocrine tumors are on the rise: epidemiological changes in Germany. World J Gastroenterol 2013; 19: 9012-9019 DOI: 10.3748/wjg.v19.i47.9012. (PMID: 24379626)
• 4 Yao JC, Hassan M, Phan A. et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008; 26: 3063-3072 DOI: 10.1200/JCO.2007.15.4377. (PMID: 18565894)
• 5 Scoazec JY, Couvelard A, Reseau T. [Classification of pancreatic neuroendocrine tumours: Changes made in the 2017 WHO classification of tumours of endocrine organs and perspectives for the future]. Ann Pathol 2017; 37: 444-456 DOI: 10.1016/j.annpat.2017.10.003.
• 6 Pape UF, Berndt U, Muller-Nordhorn J. et al. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer 2008; 15: 1083-1097 DOI: 10.1677/ERC-08-0017. (PMID: 18603570)
• 7 Scherubl H, Raue F, Frank-Raue K. [Neuroendocrine tumors: Classification, clinical presentation and imaging]. Radiologe 2019; 59: 952-960 DOI: 10.1007/s00117-019-0574-x. (PMID: 31359091)
• 8 Pelosi G, Sonzogni A, Harari S. et al. Classification of pulmonary neuroendocrine tumors: new insights. Transl Lung Cancer Res 2017; 6: 513-529 DOI: 10.21037/tlcr.2017.09.04. (PMID: 29114468)
• 9 Sahani DV, Bonaffini PA, Fernandez-Del Castillo C. et al. Gastroenteropancreatic neuroendocrine tumors: role of imaging in diagnosis and management. Radiology 2013; 266: 38-61 DOI: 10.1148/radiol.12112512. (PMID: 23264526)
• 10 Ter-Minassian M, Chan JA, Hooshmand SM. et al. Clinical presentation, recurrence, and survival in patients with neuroendocrine tumors: results from a prospective institutional database. Endocr Relat Cancer 2013; 20: 187-196 DOI: 10.1530/ERC-12-0340. (PMID: 23319495)
• 11 Halperin DM, Shen C, Dasari A. et al. Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: a population-based study. Lancet Oncol 2017; 18: 525-534 DOI: 10.1016/S1470-2045(17)30110-9. (PMID: 28238592)
• 12 Pinchot SN, Holen K, Sippel RS. et al. Carcinoid tumors. Oncologist 2008; 13: 1255-1269 DOI: 10.1634/theoncologist.2008-0207. (PMID: 19091780)
• 13 Shah MH, Goldner WS, Benson AB. et al. Neuroendocrine and Adrenal Tumors, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19: 839-868 DOI: 10.6004/jnccn.2021.0032. (PMID: 34340212)
• 14 Basuroy R, Srirajaskanthan R, Ramage JK. Neuroendocrine Tumors. Gastroenterol Clin North Am 2016; 45: 487-507 DOI: 10.1016/j.gtc.2016.04.007. (PMID: 27546845)
• 15 Pirasteh A, Lovrec P, Bodei L. Imaging of neuroendocrine tumors: A pictorial review of the clinical value of different imaging modalities. Rev Endocr Metab Disord 2021; 22: 539-552 DOI: 10.1007/s11154-021-09631-7. (PMID: 33783695)
• 16 Sundin A. Radiological and nuclear medicine imaging of gastroenteropancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol 2012; 26: 803-818 DOI: 10.1016/j.bpg.2012.12.004. (PMID: 23582920)
• 17 Kos-Kudla B, Blicharz-Dorniak J, Strzelczyk J. et al. Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours). Endokrynol Pol 2017; 68: 79-110 DOI: 10.5603/EP.2017.0015. (PMID: 28597909)
• 18 James PD, Tsolakis AV, Zhang M. et al. Incremental benefit of preoperative EUS for the detection of pancreatic neuroendocrine tumors: a meta-analysis. Gastrointest Endosc 2015; 81: 848-856.e1 DOI: 10.1016/j.gie.2014.12.031. (PMID: 25805462)
• 19 van Asselt SJ, Brouwers AH, van Dullemen HM. et al. EUS is superior for detection of pancreatic lesions compared with standard imaging in patients with multiple endocrine neoplasia type 1. Gastrointest Endosc 2015; 81: 159-167.e2 DOI: 10.1016/j.gie.2014.09.037. (PMID: 25527055)
• 20 Poltorak-Szymczak G, Budlewski T, Furmanek MI. et al. Radiological Imaging of Gastro-Entero-Pancreatic Neuroendocrine Tumors. The Review of Current Literature Emphasizing the Diagnostic Value of Chosen Imaging Methods. Front Oncol 2021; 11: 670233 DOI: 10.3389/fonc.2021.670233. (PMID: 34211845)
• 21 Del Prete M, Di Sarno A, Modica R. et al. Role of contrast-enhanced ultrasound to define prognosis and predict response to biotherapy in pancreatic neuroendocrine tumors. J Endocrinol Invest 2017; 40: 1373-1380 DOI: 10.1007/s40618-017-0723-x. (PMID: 28667452)
• 22 Piscaglia F, Sansone V, Tovoli F. Contrast-enhanced ultrasound of the liver in colorectal cancer: A useful tool in the right patient. J Hepatol 2021; 74: 272-273 DOI: 10.1016/j.jhep.2020.11.044.
• 23 Park HJ, Kim HJ, Kim KW. et al. Comparison between neuroendocrine carcinomas and well-differentiated neuroendocrine tumors of the pancreas using dynamic enhanced CT. Eur Radiol 2020; 30: 4772-4782 DOI: 10.1007/s00330-020-06867-w. (PMID: 32346794)
• 24 Sundin A, Arnold R, Baudin E. et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological, Nuclear Medicine & Hybrid Imaging. Neuroendocrinology 2017; 105: 212-244 DOI: 10.1159/000471879. (PMID: 28355596)
• 25 Desai H, Borges-Neto S, Wong TZ. Molecular Imaging and Therapy for Neuroendocrine Tumors. Curr Treat Options Oncol 2019; 20: 78 DOI: 10.1007/s11864-019-0678-6. (PMID: 31468190)
• 26 Granata V, Fusco R, Setola SV. et al. The multidisciplinary team for gastroenteropancreatic neuroendocrine tumours: the radiologist’s challenge. Radiol Oncol 2019; 53: 373-387 DOI: 10.2478/raon-2019-0040. (PMID: 31652122)
• 27 Ramirez-Renteria C, Ferreira-Hermosillo A, Marrero-Rodriguez D. et al. An Update on Gastroenteropancreatic Neuroendocrine Neoplasms: From Mysteries to Paradigm Shifts. Arch Med Res 2020; 51: 765-776 DOI: 10.1016/j.arcmed.2020.06.018. (PMID: 32654882)
• 28 Dromain C, de Baere T, Lumbroso J. et al. Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging. J Clin Oncol 2005; 23: 70-78 DOI: 10.1200/JCO.2005.01.013. (PMID: 15625361)
• 29 Dromain C, de Baere T, Baudin E. et al. MR imaging of hepatic metastases caused by neuroendocrine tumors: comparing four techniques. AJR Am J Roentgenol 2003; 180: 121-128 DOI: 10.2214/ajr.180.1.1800121. (PMID: 12490490)
• 30 d’Assignies G, Fina P, Bruno O. et al. High sensitivity of diffusion-weighted MR imaging for the detection of liver metastases from neuroendocrine tumors: comparison with T2- weighted and dynamic gadolinium-enhanced MR imaging. Radiology 2013; 268: 390-399 DOI: 10.1148/radiol.13121628. (PMID: 23533288)
• 31 Liapi E, Geschwind JF, Vossen JA. et al. Functional MRI evaluation of tumor response in patients with neuroendocrine hepatic metastasis treated with transcatheter arterial chemoembolization. AJR Am J Roentgenol 2008; 190: 67-73 DOI: 10.2214/ajr.07.2550. (PMID: 18094295)
• 32 Ingenerf M, Kiesl S, Karim S. et al. (68)Ga-DOTATATE PET/CT and MRI with diffusion-weighted imaging (DWI) in shortand long-term assessment of tumor response of neuroendocrine liver metastases (NELM) following transarterial radioembolization (TARE). Cancers (Basel) 2021; DOI: 10.3390/cancers13174321.
• 33 Baumann T, Rottenburger C, Nicolas G. et al. Gastroenteropancreatic neuroendocrine tumours (GEP-NET) – Imaging and staging. Best Pract Res Clin Endocrinol Metab 2016; 30: 45-57 DOI: 10.1016/j.beem.2016.01.003. (PMID: 26971843)
• 34 Lee L, Ito T, Jensen RT. Imaging of pancreatic neuroendocrine tumors: recent advances, current status, and controversies. Expert Rev Anticancer Ther 2018; 18: 837-860 DOI: 10.1080/14737140.2018.1496822. (PMID: 29973077)
• 35 Barat M, Soyer P, Al Sharhan F. et al. MRI may be able to identify the origin of neuroendocrine tumor liver metastases. euroendocrinology 2020; DOI: 10.1159/000513015.
• 36 Bozkurt MF, Virgolini I, Balogova S. 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: 1588-1601 DOI: 10.1007/s00259-017-3728-y. (PMID: 28547177)
• 37 de Herder WW, Hofland LJ, van der Lely AJ. et al. Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours. Endocr Relat Cancer 2003; 10: 451-458 DOI: 10.1677/erc.0.0100451. (PMID: 14713257)
• 38 Ilhan H, Lindner S, Todica A. et al. Biodistribution and first clinical results of (18)F-SiFAlin-TATE PET: a novel (18)F-labeled somatostatin analog for imaging of neuroendocrine tumors. Eur J Nucl Med Mol Imaging 2020; 47: 870-880 DOI: 10.1007/s00259-019-04501-6. (PMID: 31492994)
• 39 Pauwels E, Cleeren F, Tshibangu T. et al. Al(18)F-NOTA-octreotide: first comparison with (68)Ga-DOTATATE in a neuroendocrine tumour patient. Eur J Nucl Med Mol Imaging 2019; 46: 2398-2399 DOI: 10.1007/s00259-019-04425-1. (PMID: 31367905)
• 40 Basu S, Adnan A. Well-differentiated grade 3 neuroendocrine tumours and poorly differentiated grade 3 neuroendocrine carcinomas: will dual tracer PET-computed tomography (68Ga-DOTATATE and FDG) play a pivotal role in differentiation and guiding management strategies?. Nucl Med Commun 2019; 40: 1086-1087 DOI: 10.1097/MNM0000000000001072. (PMID: 31365493)
• 41 Zhang J, Liu Q, Singh A. et al. Prognostic Value of (18)F-FDG PET/CT in a Large Cohort of Patients with Advanced Metastatic Neuroendocrine Neoplasms Treated with Peptide Receptor Radionuclide Therapy. J Nucl Med 2020; 61: 1560-1569 DOI: 10.2967/jnumed.119.241414. (PMID: 32169914)
• 42 Flavell RR, Naeger DM, Aparici CM. et al. Malignancies with Low Fluorodeoxyglucose Uptake at PET/CT: Pitfalls and Prognostic Importance: Resident and Fellow Education Feature. Radiographics 2016; 36: 293-294 DOI: 10.1148/rg.2016150073. (PMID: 26761542)
• 43 Sheikhbahaei S, Sadaghiani MS, Rowe SP. et al. Neuroendocrine Tumor Theranostics: An Update and Emerging Applications in Clinical Practice. AJR Am J Roentgenol 2021; 217: 495-506 DOI: 10.2214/AJR.20.23349. (PMID: 34076455)
• 44 Deppen SA, Blume J, Bobbey AJ. 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: 872-878 DOI: 10.2967/jnumed.115.165803. (PMID: 26769864)
• 45 Froelich MF, Schnitzer ML, Holzgreve A. et al. Cost-Effectiveness Analysis of (68)Ga DOTA-TATE PET/CT, (111)In-Pentetreotide SPECT/CT and CT for Diagnostic Workup of Neuroendocrine Tumors. Diagnostics (Basel) 2021; DOI: 10.3390/diagnostics11020334.
• 46 Hofman MS, Lau WF, Hicks RJ. Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics 2015; 35: 500-516 DOI: 10.1148/rg.352140164. (PMID: 25763733)
• 47 Jacobsson H, Larsson P, Jonsson C. et al. Normal uptake of 68Ga-DOTA-TOC by the pancreas uncinate process mimicking malignancy at somatostatin receptor PET. Clin Nucl Med 2012; 37: 362-365 DOI: 10.1097/RLU.0b013e3182485110. (PMID: 22391705)
• 48 Pirasteh A, Riedl C, Mayerhoefer ME. et al. PET/MRI for neuroendocrine tumors: a match made in heaven or just another hype?. Clin Transl Imaging 2019; 7: 405-413 DOI: 10.1007/s40336-019-00344-1. (PMID: 33282794)
• 49 Olsen JO, Pozderac RV, Hinkle G. et al. Somatostatin receptor imaging of neuroendocrine tumors with indium-111 pentetreotide (Octreoscan). Semin Nucl Med 1995; 25: 251-261 DOI: 10.1016/s0001-2998(95)80014-x. (PMID: 7570044)
• 50 Hennrich U, Benesova M. [(68)Ga]Ga-DOTA-TOC: The First FDA-Approved (68)Ga-Radiopharmaceutical for PET Imaging. Pharmaceuticals (Basel) 2020; DOI: 10.3390/ph13030038.
• 51 Beyer L, Gosewisch A, Lindner S. et al. Dosimetry and optimal scan time of [(18)F]SiTATE-PET/CT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2021; DOI: 10.1007/s00259-021-05351-x.
• 52 Lottes G, Schober O. Costs of F-18-FDG PET with a satellite concept: update. Nuklearmedizin 2000; 39: 72-76 (PMID: 10834194)
• 53 Werner RA, Bluemel C, Allen-Auerbach MS. et al. 68Gallium- and 90Yttrium-/177Lutetium: “theranostic twins” for diagnosis and treatment of NETs. Ann Nucl Med 2015; 29: 1-7 DOI: 10.1007/s12149-014-0898-6. (PMID: 25139472)
• 54 Mullard A. 2016 FDA drug approvals. Nat Rev Drug Discov 2017; 16: 73-76 DOI: 10.1038/nrd.2017.14. (PMID: 28148938)