Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 3/2015

01-03-2015 | Original Article

18F-FDOPA PET/CT imaging of insulinoma revisited

Authors: Alessio Imperiale, Frédéric Sebag, Michel Vix, Frédéric Castinetti, Laurence Kessler, François Moreau, Philippe Bachellier, Benjamin Guillet, Izzie-Jacques Namer, Olivier Mundler, David Taïeb

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2015

Login to get access

Abstract

Purpose

18F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to 18F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with 18F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population.

Methods

A retrospective study including 16 HH patients who were investigated between January 2011 and December 2013 using 18F-FDOPA PET/CT (17 examinations) in two academic endocrine tumour centres was conducted. All PET/CT examinations were performed under CD premedication (200 mg orally, 1 – 2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after 18F-FDOPA injection) centred over the upper abdomen and a delayed whole-body acquisition starting 20 – 30 min later. An independent series of eight consecutive patients with HH and investigated before 2011 were considered for comparison. All patients had a reference whole-body PET/CT scan performed about 1 h after 18F-FDOPA injection. In all cases, PET/CT was performed without CD premedication.

Results

In the study group, 18F-FDOPA PET/CT with CD premedication was positive in 8 out of 11 patients with histologically proven insulinoma (73 %). All 18F-FDOPA PET/CT-avid insulinomas were detected on early images and 5 of 11 (45 %) on delayed ones. The tumour/normal pancreas uptake ratio was not significantly different between early and delayed acquisitions. Considering all patients with HH, including those without imaging evidence of disease, the detection rate of the primary lesions using CD-assisted 18F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17 studies performed. In the control group (without CD premedication, eight patients), the final diagnosis was benign insulinoma in four, nesidioblastosis in one, and no definitive diagnosis in the remainder. 18F-FDOPA PET/CT failed to detect any tumour in these patients.

Conclusion

According to our experience, CD administration before 18F-FDOPA injection leads to low residual pancreatic 18F-FDOPA activity preserving tumoral uptake with consequent insulinoma detection in more than half of adult patients with HH and more than 70 % of patients with a final diagnosis of insulinoma. If 18F-FDOPA PET/CT is indicated, we strongly recommend combining CD premedication with early acquisition centred over the pancreas.
Literature
1.
go back to reference Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94:709–28. doi:10.1210/jc.2008-1410.CrossRefPubMed Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94:709–28. doi:10.​1210/​jc.​2008-1410.CrossRefPubMed
2.
go back to reference Zimmer T, Stolzel U, Bader M, Koppenhagen K, Hamm B, Buhr H, et al. Endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localisation of insulinomas and gastrinomas. Gut. 1996;39:562–8.CrossRefPubMedCentralPubMed Zimmer T, Stolzel U, Bader M, Koppenhagen K, Hamm B, Buhr H, et al. Endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localisation of insulinomas and gastrinomas. Gut. 1996;39:562–8.CrossRefPubMedCentralPubMed
3.
5.
go back to reference Guettier JM, Kam A, Chang R, Skarulis MC, Cochran C, Alexander HR, et al. Localization of insulinomas to regions of the pancreas by intraarterial calcium stimulation: the NIH experience. J Clin Endocrinol Metab. 2009;94:1074–80.CrossRefPubMedCentralPubMed Guettier JM, Kam A, Chang R, Skarulis MC, Cochran C, Alexander HR, et al. Localization of insulinomas to regions of the pancreas by intraarterial calcium stimulation: the NIH experience. J Clin Endocrinol Metab. 2009;94:1074–80.CrossRefPubMedCentralPubMed
6.
go back to reference Kaltsas GA, Besser GM, Grossman AB. The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev. 2004;25:458–511.CrossRefPubMed Kaltsas GA, Besser GM, Grossman AB. The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev. 2004;25:458–511.CrossRefPubMed
7.
go back to reference Kwekkeboom DJ, Krenning EP, Scheidhauer K, Lewington V, Lebtahi R, Grossman A, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: somatostatin receptor imaging with (111)In-pentetreotide. Neuroendocrinology. 2009;90:184–9. doi:10.1159/000225946.CrossRefPubMed Kwekkeboom DJ, Krenning EP, Scheidhauer K, Lewington V, Lebtahi R, Grossman A, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: somatostatin receptor imaging with (111)In-pentetreotide. Neuroendocrinology. 2009;90:184–9. doi:10.​1159/​000225946.CrossRefPubMed
8.
go back to reference Sharma P, Arora S, Karunanithi S, Khadgawat R, Durgapal P, Sharma R, et al. Somatostatin receptor based PET/CT imaging with 68Ga-DOTA-Nal3-Octreotide for localisation of clinically and biochemically suspected insulinoma. Q J Nucl Med Mol Imaging. 2014. Sharma P, Arora S, Karunanithi S, Khadgawat R, Durgapal P, Sharma R, et al. Somatostatin receptor based PET/CT imaging with 68Ga-DOTA-Nal3-Octreotide for localisation of clinically and biochemically suspected insulinoma. Q J Nucl Med Mol Imaging. 2014.
9.
10.
go back to reference Wild D, Macke H, Christ E, Gloor B, Reubi JC. Glucagon-like peptide 1-receptor scans to localize occult insulinomas. N Engl J Med. 2008;359:766–8.CrossRefPubMed Wild D, Macke H, Christ E, Gloor B, Reubi JC. Glucagon-like peptide 1-receptor scans to localize occult insulinomas. N Engl J Med. 2008;359:766–8.CrossRefPubMed
12.
go back to reference Kauhanen S, Seppanen M, Minn H, Gullichsen R, Salonen A, Alanen K, 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;92:1237–44.CrossRefPubMed Kauhanen S, Seppanen M, Minn H, Gullichsen R, Salonen A, Alanen K, 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;92:1237–44.CrossRefPubMed
13.
go back to reference Tessonnier L, Sebag F, Ghander C, De Micco C, Reynaud R, Palazzo FF, et al. Limited value of 18F-F-DOPA PET to localize pancreatic insulin-secreting tumors in adults with hyperinsulinemic hypoglycemia. J Clin Endocrinol Metab. 2010;95:303–7. doi:10.1210/jc.2009-1357.CrossRefPubMed Tessonnier L, Sebag F, Ghander C, De Micco C, Reynaud R, Palazzo FF, et al. Limited value of 18F-F-DOPA PET to localize pancreatic insulin-secreting tumors in adults with hyperinsulinemic hypoglycemia. J Clin Endocrinol Metab. 2010;95:303–7. doi:10.​1210/​jc.​2009-1357.CrossRefPubMed
14.
go back to reference Orlefors H, Sundin A, Lu L, Oberg K, Langstrom B, Eriksson B, et al. Carbidopa pretreatment improves image interpretation and visualisation of carcinoid tumours with 11C-5-hydroxytryptophan positron emission tomography. Eur J Nucl Med Mol Imaging. 2006;33:60–5. doi:10.1007/s00259-005-1891-z.CrossRefPubMed Orlefors H, Sundin A, Lu L, Oberg K, Langstrom B, Eriksson B, et al. Carbidopa pretreatment improves image interpretation and visualisation of carcinoid tumours with 11C-5-hydroxytryptophan positron emission tomography. Eur J Nucl Med Mol Imaging. 2006;33:60–5. doi:10.​1007/​s00259-005-1891-z.CrossRefPubMed
15.
go back to reference Neels OC, Koopmans KP, Jager PL, Vercauteren L, van Waarde A, Doorduin J, et al. Manipulation of [11C]-5-hydroxytryptophan and 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine accumulation in neuroendocrine tumor cells. Cancer Res. 2008;68:7183–90. doi:10.1158/0008-5472.CAN-08-0095.CrossRefPubMed Neels OC, Koopmans KP, Jager PL, Vercauteren L, van Waarde A, Doorduin J, et al. Manipulation of [11C]-5-hydroxytryptophan and 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine accumulation in neuroendocrine tumor cells. Cancer Res. 2008;68:7183–90. doi:10.​1158/​0008-5472.​CAN-08-0095.CrossRefPubMed
16.
go back to reference Imperiale A, Rust E, Gabriel S, Detour J, Goichot B, Duclos B, et al. 18F-fluorodihydroxyphenylalanine PET/CT in patients with neuroendocrine tumors of unknown origin: relation to tumor origin and differentiation. J Nucl Med. 2014;55:367–72. doi:10.2967/jnumed.113.126896.CrossRefPubMed Imperiale A, Rust E, Gabriel S, Detour J, Goichot B, Duclos B, et al. 18F-fluorodihydroxyphenylalanine PET/CT in patients with neuroendocrine tumors of unknown origin: relation to tumor origin and differentiation. J Nucl Med. 2014;55:367–72. doi:10.​2967/​jnumed.​113.​126896.CrossRefPubMed
17.
go back to reference 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;26:1489–95. doi:10.1200/JCO.2007.15.1126.CrossRefPubMed 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;26:1489–95. doi:10.​1200/​JCO.​2007.​15.​1126.CrossRefPubMed
18.
go back to reference Kauhanen S, Seppanen M, Nuutila P. Premedication with carbidopa masks positive finding of insulinoma and beta-cell hyperplasia in [18F]-dihydroxy-phenyl-alanine positron emission tomography. J Clin Oncol. 2008;26:5307–8. doi:10.1200/JCO.2008.18.8581. author reply 8–9.CrossRefPubMed Kauhanen S, Seppanen M, Nuutila P. Premedication with carbidopa masks positive finding of insulinoma and beta-cell hyperplasia in [18F]-dihydroxy-phenyl-alanine positron emission tomography. J Clin Oncol. 2008;26:5307–8. doi:10.​1200/​JCO.​2008.​18.​8581. author reply 8–9.CrossRefPubMed
19.
go back to reference Kauhanen S, Seppanen M, Minn H, Nuutila P. Clinical PET imaging of insulinoma and beta-cell hyperplasia. Curr Pharm Des. 2010;16:1550–60.CrossRefPubMed Kauhanen S, Seppanen M, Minn H, Nuutila P. Clinical PET imaging of insulinoma and beta-cell hyperplasia. Curr Pharm Des. 2010;16:1550–60.CrossRefPubMed
21.
go back to reference Beuthien-Baumann B, Strumpf A, Zessin J, Bredow J, Kotzerke J. Diagnostic impact of PET with 18F-FDG, 18F-DOPA and 3-O-methyl-6-[18F]fluoro-DOPA in recurrent or metastatic medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2007;34:1604–9. doi:10.1007/s00259-007-0425-2.CrossRefPubMed Beuthien-Baumann B, Strumpf A, Zessin J, Bredow J, Kotzerke J. Diagnostic impact of PET with 18F-FDG, 18F-DOPA and 3-O-methyl-6-[18F]fluoro-DOPA in recurrent or metastatic medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2007;34:1604–9. doi:10.​1007/​s00259-007-0425-2.CrossRefPubMed
22.
go back to reference Koopmans KP, de Groot JW, Plukker JT, de Vries EG, Kema IP, Sluiter WJ, et al. 18F-dihydroxyphenylalanine PET in patients with biochemical evidence of medullary thyroid cancer: relation to tumor differentiation. J Nucl Med. 2008;49:524–31. doi:10.2967/jnumed.107.047720.CrossRefPubMed Koopmans KP, de Groot JW, Plukker JT, de Vries EG, Kema IP, Sluiter WJ, et al. 18F-dihydroxyphenylalanine PET in patients with biochemical evidence of medullary thyroid cancer: relation to tumor differentiation. J Nucl Med. 2008;49:524–31. doi:10.​2967/​jnumed.​107.​047720.CrossRefPubMed
24.
go back to reference Barthlen W, Blankenstein O, Mau H, Koch M, Hohne C, Mohnike W, et al. Evaluation of [18F]fluoro-L-DOPA positron emission tomography-computed tomography for surgery in focal congenital hyperinsulinism. J Clin Endocrinol Metab. 2008;93:869–75. doi:10.1210/jc.2007-2036.CrossRefPubMed Barthlen W, Blankenstein O, Mau H, Koch M, Hohne C, Mohnike W, et al. Evaluation of [18F]fluoro-L-DOPA positron emission tomography-computed tomography for surgery in focal congenital hyperinsulinism. J Clin Endocrinol Metab. 2008;93:869–75. doi:10.​1210/​jc.​2007-2036.CrossRefPubMed
25.
go back to reference de Lonlay P, Simon-Carre A, Ribeiro MJ, Boddaert N, Giurgea I, Laborde K, et al. Congenital hyperinsulinism: pancreatic [18F]fluoro-L-dihydroxyphenylalanine (DOPA) positron emission tomography and immunohistochemistry study of DOPA decarboxylase and insulin secretion. J Clin Endocrinol Metab. 2006;91:933–40. doi:10.1210/jc.2005-1713.CrossRefPubMed de Lonlay P, Simon-Carre A, Ribeiro MJ, Boddaert N, Giurgea I, Laborde K, et al. Congenital hyperinsulinism: pancreatic [18F]fluoro-L-dihydroxyphenylalanine (DOPA) positron emission tomography and immunohistochemistry study of DOPA decarboxylase and insulin secretion. J Clin Endocrinol Metab. 2006;91:933–40. doi:10.​1210/​jc.​2005-1713.CrossRefPubMed
26.
go back to reference Hardy OT, Hernandez-Pampaloni M, Saffer JR, Suchi M, Ruchelli E, Zhuang H, et al. Diagnosis and localization of focal congenital hyperinsulinism by 18F-fluorodopa PET scan. J Pediatr. 2007;150:140–5.CrossRefPubMed Hardy OT, Hernandez-Pampaloni M, Saffer JR, Suchi M, Ruchelli E, Zhuang H, et al. Diagnosis and localization of focal congenital hyperinsulinism by 18F-fluorodopa PET scan. J Pediatr. 2007;150:140–5.CrossRefPubMed
27.
go back to reference Otonkoski T, Nanto-Salonen K, Seppanen M, Veijola R, Huopio H, Hussain K, et al. Noninvasive diagnosis of focal hyperinsulinism of infancy with [18F]-DOPA positron emission tomography. Diabetes. 2006;55:13–8.CrossRefPubMed Otonkoski T, Nanto-Salonen K, Seppanen M, Veijola R, Huopio H, Hussain K, et al. Noninvasive diagnosis of focal hyperinsulinism of infancy with [18F]-DOPA positron emission tomography. Diabetes. 2006;55:13–8.CrossRefPubMed
28.
go back to reference Ribeiro MJ, Boddaert N, Bellanne-Chantelot C, Bourgeois S, Valayannopoulos V, Delzescaux T, et al. The added value of [18F]fluoro-L-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children. Eur J Nucl Med Mol Imaging. 2007;34:2120–8. doi:10.1007/s00259-007-0498-y.CrossRefPubMed Ribeiro MJ, Boddaert N, Bellanne-Chantelot C, Bourgeois S, Valayannopoulos V, Delzescaux T, et al. The added value of [18F]fluoro-L-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children. Eur J Nucl Med Mol Imaging. 2007;34:2120–8. doi:10.​1007/​s00259-007-0498-y.CrossRefPubMed
29.
go back to reference Ribeiro MJ, De Lonlay P, Delzescaux T, Boddaert N, Jaubert F, Bourgeois S, et al. Characterization of hyperinsulinism in infancy assessed with PET and 18F-fluoro-L-DOPA. J Nucl Med. 2005;46:560–6.PubMed Ribeiro MJ, De Lonlay P, Delzescaux T, Boddaert N, Jaubert F, Bourgeois S, et al. Characterization of hyperinsulinism in infancy assessed with PET and 18F-fluoro-L-DOPA. J Nucl Med. 2005;46:560–6.PubMed
30.
go back to reference Timmers HJ, Hadi M, Carrasquillo JA, Chen CC, Martiniova L, Whatley M, et al. The effects of carbidopa on uptake of 6-18F-fluoro-L-DOPA in PET of pheochromocytoma and extraadrenal abdominal paraganglioma. J Nucl Med. 2007;48:1599–606.CrossRefPubMed Timmers HJ, Hadi M, Carrasquillo JA, Chen CC, Martiniova L, Whatley M, et al. The effects of carbidopa on uptake of 6-18F-fluoro-L-DOPA in PET of pheochromocytoma and extraadrenal abdominal paraganglioma. J Nucl Med. 2007;48:1599–606.CrossRefPubMed
32.
Metadata
Title
18F-FDOPA PET/CT imaging of insulinoma revisited
Authors
Alessio Imperiale
Frédéric Sebag
Michel Vix
Frédéric Castinetti
Laurence Kessler
François Moreau
Philippe Bachellier
Benjamin Guillet
Izzie-Jacques Namer
Olivier Mundler
David Taïeb
Publication date
01-03-2015
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2015
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-014-2943-z

Other articles of this Issue 3/2015

European Journal of Nuclear Medicine and Molecular Imaging 3/2015 Go to the issue