Einsatz der Positronen-Emissions-Tomografie bei ­neuroendokrinen Tumoren

Zusammenfassung

Neuroendokrine Tumoren (NET) sind eine genetisch heterogene Gruppe von Tumoren mit malignem Potenzial, die eine große klinische Variation aufweisen. Die Klassifikation basiert unter anderem auf der proliferativen Aktivität, wobei G1-Tumoren einen Proliferationsindex von ≤ 2%, G2-Tumoren einen von 3–20% und G3-Tumoren einen von > 20% aufweisen. Molekulare bildgebende Verfahren basieren großteils auf der Eigenschaft von hoher Somatostatinrezeptorexpression. Von den 5 bekannten Rezeptorsubtypen spielt der Subtyp 2 die größte Rolle. PET/CT mit ⁶⁸Gallium markierten Somatostatinanaloga ist zumindest an großen Zentren die Bildgebung der ersten Wahl. Die wichtigsten Vorteile gegenüber konventioneller Szintigrafie sind verbesserte Sensitivität und Spezifität, kurze Aufnahmeprotokolle und die Möglichkeit einer zuverlässigen Uptake-Quantifizierung. Des Weiteren sind in der klinischen Routine PET-Tracer, die z. B. den Glukosemetabolismus oder Amine-precurser-Metabolismus abbilden, verfügbar, die bei vielen Fragestellungen eine hohe klinische Wertigkeit aufweisen.

Abstract

Neuroendocrine tumours (NETs) are a genetically diverse group of diseases with malignant potential, displaying a great variability in clinical outcome. They are classified into well differentiated neuroendocrine tumors or carcinomas (proliferation index ≤ 2%), well-differentiated neuroendocrine carcinoma (proliferation index 3–20%) and poorly differentiated neuroendocrine carcinoma (proliferation index > 20%). The molecular imaging of NETs is strongly based on the property of these tumor cells to express somatostatin receptors which appear in 5 subtypes, SSTR 1–5 with the subtype 2 being predominant. Gallium-68 labeled somatostatin analogue PET/CT is an increasingly applied method for staging and restaging of patients with neuroendocrine carcinomas. Key advantages over conventional scintigraphy are increased sensitivity and specificity, short scanning protocols and the possibility of accurate uptake quantification. Additionally, a wide variety of routinely used functional imaging is able to characterise NETs for example in regard of glucose metabolism and amine-precurser metabolism with clinical impact in staging, therapy monitoring and prognosis.

Schlüsselwörter

68-Gallium - Somatostatinanaloga - PET/CT - neuroendokrine Tumoren

Key words

68-Gallium - somatostatin analogue - PET/CT - neuroendocrine tumors

• Literatur

• 1 Al-Ibraheem A, Bundschuh RA, Notni J et al. Focal uptake of (68)Ga-DOTATOC in the pancreas: pathological or physiological correlate in patients with neuroendocrine tumours?. Eur J Nucl Med Mol Imaging 2011; 38: 2005-2013
• 2 Binderup T, Knigge U, Loft A et al. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET. J Nucl Med 2010; 51: 704-712
• 3 Binderup T, Knigge U, Loft A et al. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res 2010; 16: 978-985
• 4 Breeman WA, de Jong M, de Blois E et al. Radiolabelling DOTA-peptides with 68Ga. Eur J Nucl Med Mol Imaging 2005; 32: 478-485
• 5 Buchmann I, Henze M, Engelbrecht S 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: 1617-1626
• 6 Castellucci P, Pou Ucha J, Fuccio C et al. Incidence of increased 68Ga-DOTANOC uptake in the pancreatic head in a large series of extrapancreatic NET patients studied with sequential PET/CT. J Nucl Med 2011; 52: 886-890
• 7 Fottner C, Helisch A, Anlauf M et al. 6-18F-fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to 123I-metaiodo­benzyl-guanidine scintigraphy in the detection of extraadrenal and hereditary pheochromocytomas and paragangliomas: correlation with vesicular monoamine transporter expression. J Clin Endocrinol Metab 2010; 95: 2800-2810
• 8 Gabriel M, Decristoforo C, Kendler D et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 2007; 48: 508-518
• 9 Haug AR, Auernhammer CJ, Wangler B et al. 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: 1349-1356
• 10 Kaemmerer D, Peter L, Lupp A et al. Molecular imaging with Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2011; 38: 1659-1668
• 11 Kauhanen S, Seppanen M, Minn H et al. Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography as a tool to localize an insulinoma or beta-cell hyperplasia in adult patients. J Clin Endocrinol Metab 2007; 92: 1237-1244
• 12 King KS, Chen CC, Alexopoulos DK et al. Functional imaging of SDHx-related head and neck paragangliomas: comparison of 18F-fluorodihydroxyphenylalanine, 18F-fluorodopamine, 18F-fluoro-2-deoxy-D-glucose PET, 123I-metaiodobenzylguanidine scintigraphy, and 111In-pentetreotide scintigraphy. J Clin Endocrinol Metab 2011; 96: 2779-2785
• 13 Krausz Y, Freedman N, Rubinstein R et al. 68Ga-DOTA-NOC PET/CT imaging of neuroendocrine tumors: comparison with (1)(1)(1)In-DTPA-octreotide (OctreoScan(R)). Mol Imaging Biol 2011; 13: 583-593
• 14 Kroiss A, Putzer D, Uprimny C et al. 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: 865-873
• 15 Miederer M, Seidl S, Buck A et al. 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: 48-52
• 16 Rindi G, Kloppel G, Alhman H et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2006; 449: 395-401
• 17 Rindi G, Kloppel G, Couvelard A et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2007; 451: 757-762