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Published in: European Journal of Nuclear Medicine and Molecular Imaging 9/2016

Open Access 01-08-2016 | Original Article

Direct comparison of 68Ga-DOTA-TOC and 18F-FDG PET/CT in the follow-up of patients with neuroendocrine tumour treated with the first full peptide receptor radionuclide therapy cycle

Authors: Bernhard Nilica, Dietmar Waitz, Vlado Stevanovic, Christian Uprimny, Dorota Kendler, Sabine Buxbaum, Boris Warwitz, Llanos Gerardo, Benjamin Henninger, Irene Virgolini, Margarida Rodrigues

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2016

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Abstract

Purpose

To determine the value of 68Ga-DOTA-TOC and 18F-FDG PET/CT for initial and follow-up evaluation of patients with neuroendocrine tumour (NET) treated with peptide receptor radionuclide therapy (PRRT).

Methods

We evaluated 66 patients who had histologically proven NET and underwent both PRRT and three combined 68Ga-DOTA-TOC and 18F-FDG PET/CT studies. 68Ga-DOTA-TOC PET/CT was performed before PRRT, 3 months after completion of PRRT and after a further 6 – 9 months. 18F-FDG PET/CT was done within 2 months of 68Ga-DOTA-TOC PET/CT. Follow-up ranged from 11.8 to 80.0 months (mean 34.5 months).

Results

All patients were 68Ga-DOTA-TOC PET-positive initially and at follow-up after the first full PRRT cycle. Overall, 62 of the 198 18F-FDG PET studies (31 %) were true-positive in 38 of the 66 patients (58 %). Of the 66 patients, 28 (5 grade 1, 23 grade 2) were 18F-FDG-negative initially and during follow-up (group 1), 24 (5 grade 1, 13 grade 2, 6 grade 3) were 18F-FDG-positive initially and during follow-up (group 2), 9 patients (2 grade 1, 6 grade 2, 1 grade 3) were 18F-FDG-negative initially but 18F-FDG-positive during follow-up (group 3), and 5 patients (all grade 2) were 18F-FDG-positive initially but 18F-FDG-negative during follow-up (group 4).18F-FDG PET showed more and/or larger metastases than 68Ga-DOTA-TOC PET in five patients of group 2 and four patients of group 3, all with progressive disease. In three patients with progressive disease who died during follow-up tumour SUVmax increased by 41 – 82 % from the first to the last follow-up investigation.

Conclusion

In NET patients, the presence of 18F-FDG-positive tumours correlates strongly with a higher risk of progression. Initially, patients with 18F-FDG-negative NET may show 18F-FDG-positive tumours during follow-up. Also patients with grade 1 and grade 2 NET may have 18F-FDG-positive tumours. Therefore, 18F-FDG PET/CT is a complementary tool to 68Ga-DOTA-TOC PET/CT with clinical relevance for molecular investigation.
Literature
1.
go back to reference Reubi JC, Schar JC, Waser B, Wenger S, Heppeler A, Schmitt JS, et al. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med. 2000;27:273–82.CrossRefPubMed Reubi JC, Schar JC, Waser B, Wenger S, Heppeler A, Schmitt JS, et al. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med. 2000;27:273–82.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
3.
go back to reference Putzer D, Gabriel M, Henninger B, Kendler D, Uprimny C, Dobrozemsky G, et al. Bone metastases in patients with neuroendocrine tumor: 68Ga-DOTA-Tyr3-octreotide PET in comparison to CT and bone scintigraphy. J Nucl Med. 2009;50:1214–21.CrossRefPubMed Putzer D, Gabriel M, Henninger B, Kendler D, Uprimny C, Dobrozemsky G, et al. Bone metastases in patients with neuroendocrine tumor: 68Ga-DOTA-Tyr3-octreotide PET in comparison to CT and bone scintigraphy. J Nucl Med. 2009;50:1214–21.CrossRefPubMed
4.
go back to reference Treglia G, Castaldi P, Rindi G, Giordano A, Rufini V. Diagnostic performance of gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis. Endocrine. 2012;42:80–7.CrossRefPubMed Treglia G, Castaldi P, Rindi G, Giordano A, Rufini V. Diagnostic performance of gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis. Endocrine. 2012;42:80–7.CrossRefPubMed
5.
go back to reference Wong KK, Waterfield RT, Marzola MC, Scarsbrook AF, Chowdhury FU, Gross MD, et al. Contemporary nuclear medicine imaging of neuroendocrine tumours. Clin Radiol. 2012;67:1035–50.CrossRefPubMed Wong KK, Waterfield RT, Marzola MC, Scarsbrook AF, Chowdhury FU, Gross MD, et al. Contemporary nuclear medicine imaging of neuroendocrine tumours. Clin Radiol. 2012;67:1035–50.CrossRefPubMed
6.
go back to reference Gabriel M, Andergassen U, Putzer D, Kroiss A, Waitz D, Von Guggenberg E, et al. Individualized peptide-related-radionuclide-therapy concept using different radiolabelled somatostatin analogs in advanced cancer patients. Q J Nucl Med Mol Imaging. 2010;54:92–9.PubMed Gabriel M, Andergassen U, Putzer D, Kroiss A, Waitz D, Von Guggenberg E, et al. Individualized peptide-related-radionuclide-therapy concept using different radiolabelled somatostatin analogs in advanced cancer patients. Q J Nucl Med Mol Imaging. 2010;54:92–9.PubMed
7.
go back to reference Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA 0,Tyr3] octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26:2124–30.CrossRefPubMed Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA 0,Tyr3] octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26:2124–30.CrossRefPubMed
8.
go back to reference Öberg K, Knigge U, Kwekkeboom D, Perren A, ESMO Guidelines Working Group. Neuroendocrine gastro-entero-pancreatic tumors: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 Suppl 7:vii124–30.PubMed Öberg K, Knigge U, Kwekkeboom D, Perren A, ESMO Guidelines Working Group. Neuroendocrine gastro-entero-pancreatic tumors: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 Suppl 7:vii124–30.PubMed
9.
go back to reference Oh S, Prasad V, Lee DS, Baum RP. Effect of peptide receptor radionuclide therapy on somatostatin receptor status and glucose metabolism in neuroendocrine tumors: intraindividual comparison of Ga-68 DOTANOC PET/CT and F-18 FDG PET/CT. Int J Mol Imaging. 2011;2011:524130.CrossRefPubMedPubMedCentral Oh S, Prasad V, Lee DS, Baum RP. Effect of peptide receptor radionuclide therapy on somatostatin receptor status and glucose metabolism in neuroendocrine tumors: intraindividual comparison of Ga-68 DOTANOC PET/CT and F-18 FDG PET/CT. Int J Mol Imaging. 2011;2011:524130.CrossRefPubMedPubMedCentral
10.
go back to reference Pavel M, Baudin E, Couvelard A, Krenning E, Öberg K, Steinmüller T, et al. ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2012;95:157–76.CrossRefPubMed Pavel M, Baudin E, Couvelard A, Krenning E, Öberg K, Steinmüller T, et al. ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2012;95:157–76.CrossRefPubMed
11.
go back to reference Naswa N, Sharma P, Kumar A, Nazar AH, Kumar R, Chumber S, et al. Gallium-68-DOTA-NOC PET/CT of patients with gastroenteropancreatic neuroendocrine tumors: a prospective single-center study. AJR Am J Roentgenol. 2011;197:1221–8.CrossRefPubMed Naswa N, Sharma P, Kumar A, Nazar AH, Kumar R, Chumber S, et al. Gallium-68-DOTA-NOC PET/CT of patients with gastroenteropancreatic neuroendocrine tumors: a prospective single-center study. AJR Am J Roentgenol. 2011;197:1221–8.CrossRefPubMed
12.
go back to reference Rindi G, Arnold R, Bosman FT. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: Bosman FT, Carneiro F, Hruban RH, Theise N, editors. WHO classification of tumours of the digestive system. Lyon: IARC Press; 2010. p. 13–4. Rindi G, Arnold R, Bosman FT. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: Bosman FT, Carneiro F, Hruban RH, Theise N, editors. WHO classification of tumours of the digestive system. Lyon: IARC Press; 2010. p. 13–4.
13.
go back to reference Rindi G. The ENETS guidelines: the new TNM classification system. Tumori. 2010;96:806–9.PubMed Rindi G. The ENETS guidelines: the new TNM classification system. Tumori. 2010;96:806–9.PubMed
14.
go back to reference Strosberg J, Nasir A, Coppola D, Wick M, Kvols L. Correlation between grade and prognosis in metastatic gastroenteropancreatic neuroendocrine tumors. Hum Pathol. 2009;40:1262–8.CrossRefPubMed Strosberg J, Nasir A, Coppola D, Wick M, Kvols L. Correlation between grade and prognosis in metastatic gastroenteropancreatic neuroendocrine tumors. Hum Pathol. 2009;40:1262–8.CrossRefPubMed
15.
go back to reference Kwee TC, Basu S, Saboury B, Ambrosini V, Torigian DA, Alavi A. A new dimension of FDG-PET interpretation: assessment of tumor biology. Eur J Nucl Med Mol Imaging. 2011;38:1158–70.CrossRefPubMed Kwee TC, Basu S, Saboury B, Ambrosini V, Torigian DA, Alavi A. A new dimension of FDG-PET interpretation: assessment of tumor biology. Eur J Nucl Med Mol Imaging. 2011;38:1158–70.CrossRefPubMed
16.
go back to reference Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1, Tyr3-octreotate) and 18F-FDG. Cancer. 2008;112:2447–55.CrossRefPubMed Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1, Tyr3-octreotate) and 18F-FDG. Cancer. 2008;112:2447–55.CrossRefPubMed
17.
go back to reference Sharma P, Naswa N, Kc SS, Alvarado LA, Dwivedi AK, Yadav Y, et al. Comparison of the prognostic values of 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT in patients with well-differentiated neuroendocrine tumor. Eur J Nucl Med Mol Imaging. 2014;41:2194–202.CrossRefPubMed Sharma P, Naswa N, Kc SS, Alvarado LA, Dwivedi AK, Yadav Y, et al. Comparison of the prognostic values of 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT in patients with well-differentiated neuroendocrine tumor. Eur J Nucl Med Mol Imaging. 2014;41:2194–202.CrossRefPubMed
18.
go back to reference Basu S, Kwee TC, Gatenby R, Saboury B, Torigian DA, Alavi A. Evolving role of molecular imaging with PET in detecting and characterizing heterogeneity of cancer tissue at the primary and metastatic sites, a plausible explanation for failed attempts to cure malignant disorders. Eur J Nucl Med Mol Imaging. 2011;38:987–91.CrossRefPubMed Basu S, Kwee TC, Gatenby R, Saboury B, Torigian DA, Alavi A. Evolving role of molecular imaging with PET in detecting and characterizing heterogeneity of cancer tissue at the primary and metastatic sites, a plausible explanation for failed attempts to cure malignant disorders. Eur J Nucl Med Mol Imaging. 2011;38:987–91.CrossRefPubMed
19.
go back to reference Basu S, Sirohi B, Shrikhande SV. Dual tracer imaging approach in assessing tumor biology and heterogeneity in neuroendocrine tumors: its correlation with tumor proliferation index and possible multifaceted implications for personalized clinical management decisions, with focus on PRRT. Eur J Nucl Med Mol Imaging. 2014;41:1492–6.CrossRefPubMed Basu S, Sirohi B, Shrikhande SV. Dual tracer imaging approach in assessing tumor biology and heterogeneity in neuroendocrine tumors: its correlation with tumor proliferation index and possible multifaceted implications for personalized clinical management decisions, with focus on PRRT. Eur J Nucl Med Mol Imaging. 2014;41:1492–6.CrossRefPubMed
20.
go back to reference Belhocine T, Foidart J, Rigo P, Najjar F, Thiry A, Quatresooz P, et al. Fluorodeoxyglucose positron emission tomography and somatostatin receptor scintigraphy for diagnosing and staging carcinoid tumours: correlations with the pathological indexes p53 and Ki-67. Nucl Med Commun. 2002;23:727–34.CrossRefPubMed Belhocine T, Foidart J, Rigo P, Najjar F, Thiry A, Quatresooz P, et al. Fluorodeoxyglucose positron emission tomography and somatostatin receptor scintigraphy for diagnosing and staging carcinoid tumours: correlations with the pathological indexes p53 and Ki-67. Nucl Med Commun. 2002;23:727–34.CrossRefPubMed
21.
go back to reference Decristoforo C, Knopp R, von Guggenberg E, Rupprich M, Dreger T, Hess A, et al. A fully automated synthesis for the preparation of 68Ga-labelled peptides. Nucl Med Commun. 2007;28:870–5.CrossRefPubMed Decristoforo C, Knopp R, von Guggenberg E, Rupprich M, Dreger T, Hess A, et al. A fully automated synthesis for the preparation of 68Ga-labelled peptides. Nucl Med Commun. 2007;28:870–5.CrossRefPubMed
22.
go back to reference Hartmann H, Zöphel K, Freudenberg R, Oehme L, Andreeff M, Wunderlich G, et al. Radiation exposure of patients during 68Ga-DOTATOC PET/CT examinations. Nuklearmedizin. 2009;48:201–7.PubMed Hartmann H, Zöphel K, Freudenberg R, Oehme L, Andreeff M, Wunderlich G, et al. Radiation exposure of patients during 68Ga-DOTATOC PET/CT examinations. Nuklearmedizin. 2009;48:201–7.PubMed
23.
go back to reference Hays MT, Watson EE, Thomas SR, Stabin M. MIRD dose estimate report no. 19: radiation absorbed dose estimates from (18)F-FDG. J Nucl Med. 2002;43:210–4.PubMed Hays MT, Watson EE, Thomas SR, Stabin M. MIRD dose estimate report no. 19: radiation absorbed dose estimates from (18)F-FDG. J Nucl Med. 2002;43:210–4.PubMed
24.
25.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed
26.
go back to reference Gabriel M, Oberauer A, Dobrozemsky G, Decristoforo C, Putzer D, Kendler D, et al. 68Ga-DOTA-Tyr3-octreotide PET for assessing response to somatostatin-receptor-mediated radionuclide therapy. J Nucl Med. 2009;50:1427–34.CrossRefPubMed Gabriel M, Oberauer A, Dobrozemsky G, Decristoforo C, Putzer D, Kendler D, et al. 68Ga-DOTA-Tyr3-octreotide PET for assessing response to somatostatin-receptor-mediated radionuclide therapy. J Nucl Med. 2009;50:1427–34.CrossRefPubMed
27.
go back to reference Adams S, Baum R, Rink T, Schumm-Drager PM, Usadel KH, Hor 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 Adams S, Baum R, Rink T, Schumm-Drager PM, Usadel KH, Hor 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
28.
go back to reference Krenning EP, Valkema R, Kwekkeboom DJ, de Herder WW, van Eijck CH, de Jong M, et al. Molecular imaging as in vivo molecular pathology for gastroenteropancreatic neuroendocrine tumors: implications for follow-up after therapy. J Nucl Med. 2005;46 Suppl 1:76S–82. Krenning EP, Valkema R, Kwekkeboom DJ, de Herder WW, van Eijck CH, de Jong M, et al. Molecular imaging as in vivo molecular pathology for gastroenteropancreatic neuroendocrine tumors: implications for follow-up after therapy. J Nucl Med. 2005;46 Suppl 1:76S–82.
29.
go back to reference Binderup T, Knigge U, Loft A, Federspiel B, Kjaer A. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res. 2010;16:978–85.CrossRefPubMed Binderup T, Knigge U, Loft A, Federspiel B, Kjaer A. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res. 2010;16:978–85.CrossRefPubMed
30.
go back to reference 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;50:858–64.CrossRefPubMed 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;50:858–64.CrossRefPubMed
31.
go back to reference Arnold R, Chen YJ, Costa F, Falconi M, Gross D, Grossman AB, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: follow-up and documentation. Neuroendocrinology. 2009;90:227–33.CrossRefPubMed Arnold R, Chen YJ, Costa F, Falconi M, Gross D, Grossman AB, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: follow-up and documentation. Neuroendocrinology. 2009;90:227–33.CrossRefPubMed
32.
go back to reference O’Donoghue JA, Bardiès M, Wheldon TE. Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. J Nucl Med. 1995;36:1902–9.PubMed O’Donoghue JA, Bardiès M, Wheldon TE. Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. J Nucl Med. 1995;36:1902–9.PubMed
Metadata
Title
Direct comparison of 68Ga-DOTA-TOC and 18F-FDG PET/CT in the follow-up of patients with neuroendocrine tumour treated with the first full peptide receptor radionuclide therapy cycle
Authors
Bernhard Nilica
Dietmar Waitz
Vlado Stevanovic
Christian Uprimny
Dorota Kendler
Sabine Buxbaum
Boris Warwitz
Llanos Gerardo
Benjamin Henninger
Irene Virgolini
Margarida Rodrigues
Publication date
01-08-2016
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2016
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-016-3328-2

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