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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 1/2010

01-01-2010 | Original Article

Detection of unknown primary neuroendocrine tumours (CUP-NET) using 68Ga-DOTA-NOC receptor PET/CT

Authors: Vikas Prasad, Valentina Ambrosini, Merten Hommann, Dieter Hoersch, Stefano Fanti, Richard P. Baum

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2010

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Abstract

Purpose

This bi-centric study aimed to determine the role of receptor PET/CT using 68Ga-DOTA-NOC in the detection of undiagnosed primary sites of neuroendocrine tumours (NETs) and to understand the molecular behaviour of the primarily undiagnosed tumours.

Methods

Overall 59 patients (33 men and 26 women, age: 65 ± 9 years) with documented NET and unknown primary were enrolled. PET/CT was performed after injection of approximately 100 MBq (46–260 MBq) of 68Ga-DOTA-NOC. The maximum standardised uptake values (SUVmax) were calculated and compared with SUVmax in known pancreatic NET (pNET) and ileum/jejunum/duodenum (SI-NET). The results of PET/CT were also correlated with CT alone.

Results

In 35 of 59 patients (59%), 68Ga-DOTA-NOC PET/CT localised the site of the primary: ileum/jejunum (14), pancreas (16), rectum/colon (2), lungs (2) and paraganglioma (1). CT alone (on retrospective analyses) confirmed the findings in 12 of 59 patients (20%). The mean SUVmax of identified previously unknown pNET and SI-NET were 18.6 ± 9.8 (range: 7.8–34.8) and 9.1 ± 6.0 (range: 4.2–27.8), respectively. SUVmax in patients with previously known pNET and SI-NET were 26.1 ± 14.5 (range: 8.7–42.4) and 11.3 ± 3.7 (range: 5.6–17.9). The SUVmax of the unknown pNET and SI-NET were significantly lower (p < 0.05) as compared to the ones with known primary tumour sites; 19% of the patients had high-grade and 81% low-grade NET. Based on 68Ga-DOTA-NOC receptor PET/CT, 6 of 59 patients were operated and the primary was removed (4 pancreatic, 1 ileal and 1 rectal tumour) resulting in a management change in approximately 10% of the patients. In the remaining 29 patients, because of the far advanced stage of the disease (due to distant metastases), the primary tumours were not operated. Additional histopathological sampling was available from one patient with bronchial carcinoid (through bronchoscopy).

Conclusion

Our data indicate that 68Ga-DOTA-NOC PET/CT is highly superior to 111In-OctreoScan (39% detection rate for CUP according to the literature) and can play a major role in the management of patients with CUP-NET.
Literature
1.
Abbruzzese JL, Abbruzzese MC, Lenzi R, Hess KR, Raber MN. Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin. J Clin Oncol 1995;13:2094–103.PubMed
2.
Le Chevalier T, Cvitkovic E, Caille P, Harvey J, Contesso G, Spielmann M, et al. Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients. Arch Intern Med 1988;148:2035–9.CrossRefPubMed
3.
Didolkar MS, Fanous N, Elias EG, Moore RH. Metastatic carcinomas from occult primary tumors. A study of 254 patients. Ann Surg 1977;186:625–30.CrossRefPubMed
4.
Steckel RJ, Kagan AR. Diagnostic persistence in working up metastatic cancer with an unknown primary site. Radiology 1980;134:367–9.PubMed
5.
Briasoulis E, Pavlidis N. Cancer of unknown primary origin. Oncologist 1997;2:142–52.PubMed
6.
Hainsworth JD, Greco FA. Treatment of patients with cancer of an unknown primary site. N Engl J Med 1993;329:257–63.CrossRefPubMed
7.
McCredie M, Coates M, Churches T, Taylor R. Cancer incidence in New South Wales, Australia. Eur J Cancer 1991;27:928–31.CrossRefPubMed
8.
9.
Pavlidis N, Briasoulis E, Hainsworth J, Greco FA. Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer 2003;39:1990–2005.CrossRefPubMed
10.
Raber MN, Faintuch J, Abbruzzese JL, Sumrall C, Frost P. Continuous infusion 5-fluorouracil, etoposide and cis-diamminedichloroplatinum in patients with metastatic carcinoma of unknown primary origin. Ann Oncol 1991;2:519–20.PubMed
11.
Syed R, Bomanji JB, Nagabhushan N, Hughes S, Kayani I, Groves A, et al. Impact of combined (18)F-FDG PET/CT in head and neck tumours. Br J Cancer 2005;92:1046–50.CrossRef
12.
Alberini JL, Belhocine T, Hustinx R, Daenen F, Rigo P. Whole-body positron emission tomography using fluorodeoxyglucose in patients with metastases of unknown primary tumours (CUP syndrome). Nucl Med Commun 2003;24:1081–6.CrossRef
13.
Bohuslavizki KH, Klutmann S, Kröger S, Sonnemann U, Buchert R, Werner JA, et al. FDG PET detection of unknown primary tumors. J Nucl Med 2000;41:816–22.PubMed
14.
Freudenberg LS, Fischer M, Antoch G, Jentzen W, Gutzeit A, Rosenbaum SJ, et al. Dual modality of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography in patients with cervical carcinoma of unknown primary. Med Princ Pract 2005;14:155–60.CrossRefPubMed
15.
Gutzeit A, Antoch G, Kühl H, Egelhof T, Fischer M, Hauth E, et al. Unknown primary tumors: detection with dual-modality PET/CT—initial experience. Radiology 2005;234:227–34.CrossRefPubMed
16.
Kole AC, Nieweg OE, Pruim J, Hoekstra HJ, Koops HS, Roodenburg JL, et al. Detection of unknown occult primary tumors using positron emission tomography. Cancer 1998;82:1160–6.CrossRefPubMed
17.
Adams S, Baum R, Rink T, Schumm-Dräger PM, Usadel KH, Hör G. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med 1998;25:79–83.CrossRefPubMed
18.
Ambrosini V, Tomassetti P, Rubello D, Campana D, Nanni C, Castellucci P, et al. Role of 18F-dopa PET/CT imaging in the management of patients with 111In-pentetreotide negative GEP tumours. Nucl Med Commun 2007;28:473–7.CrossRefPubMed
19.
Baum RP, Prasad V, Hommann M, Hörsch D. Receptor PET/CT imaging of neuroendocrine tumors. Recent Results Cancer Res 2008;170:225–42.CrossRefPubMed
20.
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;35:1431–8.CrossRefPubMed
21.
Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA, et al. Processing of generator-produced 68Ga for medical application. J Nucl Med 2007;48:1741–8.CrossRefPubMed
22.
Meyer GJ, Macke H, Schuhmacher J, Knapp WH, Hofmann M. 68Ga-labelled DOTA-derivatised peptide ligands. Eur J Nucl Med Mol Imaging 2004;31:1097–104.CrossRefPubMed
23.
Neumann KH, Nystrom JS. Metastatic cancer of unknown origin: nonsquamous cell type. Semin Oncol 1982;9:427–34.PubMed
24.
Abbruzzese JL, Abbruzzese MC, Hess KR, Raber MN, Lenzi R, Frost P. Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. J Clin Oncol 1994;12:1272–80.PubMed
25.
Altman E, Cadman E. An analysis of 1539 patients with cancer of unknown primary site. Cancer 1986;57:120–4.CrossRefPubMed
26.
Moertel CG, Reitemeier RJ, Schutt AJ, Hahn RG. Treatment of the patient with adenocarcinoma of unknown origin. Cancer 1972;30:1469–72.CrossRefPubMed
27.
28.
Jensen RT. Endocrine tumors of the gastrointestinal tract and pancreas. In: Kasper DL, Fauci AS, Longo DL, et al., editors. Harrison’s principles of internal medicine. 16th ed. New York: McGraw-Hill; 2005
29.
30.
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;48:508–18.CrossRef
31.
Wild D, Mäcke HR, Waser B, Reubi JC, Ginj M, Rasch H, et al. 68Ga-DOTANOC: a first compound for PET imaging with high affinity for somatostatin receptor subtypes 2 and 5. Eur J Nucl Med Mol Imaging 2005;32:724.CrossRefPubMed
32.
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;30:1338–47.CrossRefPubMed
33.
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;28:1751–7.CrossRefPubMed
34.
Savelli G, Lucignani G, Seregni E, Marchianò A, Serafini G, Aliberti G, et al. Feasibility of somatostatin receptor scintigraphy in the detection of occult primary gastro-entero-pancreatic (GEP) neuroendocrine tumours. Nucl Med Commun 2004;25:445–9.CrossRefPubMed
35.
Hofland LJ, Lamberts SW. The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev 2003;24:28–47.CrossRefPubMed
36.
Eisenhofer G, Siegert G, Kotzerke J, Bornstein SR, Pacak K. Current progress and future challenges in the biochemical diagnosis and treatment of pheochromocytomas and paragangliomas. Horm Metab Res 2008;40:329–37.CrossRefPubMed
37.
Mundschenk J, Unger N, Schulz S, Höllt V, Schulz S, Steinke R, et al. Somatostatin receptor subtypes in human pheochromocytoma: subcellular expression pattern and functional relevance for octreotide scintigraphy. J Clin Endocrinol Metab 2003;88:5150–7.CrossRefPubMed
38.
Miederer M, Seidl S, Buck A, Scheidhauer K, Wester HJ, Schwaiger M, 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.CrossRefPubMed
39.
Zimmer T, Scherübl H, Faiss S, Stölzel U, Riecken EO, Wiedenmann B. Endoscopic ultrasonography of neuroendocrine tumours. Digestion 2000;62(Suppl 1):45–50.CrossRefPubMed
40.
Wieder H, Beer AJ, Poethko T, Meisetschlaeger G, Wester HJ, Rummeny E, et al. PET/CT with Gluc-Lys-([(18)F]FP)-TOCA: correlation between uptake, size and arterial perfusion in somatostatin receptor positive lesions. Eur J Nucl Med Mol Imaging 2008;35:264–271.CrossRefPubMed
Metadata
Title
Detection of unknown primary neuroendocrine tumours (CUP-NET) using 68Ga-DOTA-NOC receptor PET/CT
Authors
Vikas Prasad
Valentina Ambrosini
Merten Hommann
Dieter Hoersch
Stefano Fanti
Richard P. Baum
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2010
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-009-1205-y

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