18F-FDOPA PET/CT imaging of insulinoma revisited

  • Alessio Imperiale
  • Frédéric Sebag
  • Michel Vix
  • Frédéric Castinetti
  • Laurence Kessler
  • François Moreau
  • Philippe Bachellier
  • Benjamin Guillet
  • Izzie-Jacques Namer
  • Olivier Mundler
  • David Taïeb
Original Article

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.

Keywords

18F-FDOPA Carbidopa PET/CT Hyperinsulinaemic hypoglycaemia Insulinoma 

References

  1. 1.
    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.CrossRefPubMedGoogle Scholar
  2. 2.
    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.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Reubi JC, Waser B. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging. 2003;30:781–93. doi:10.1007/s00259-003-1184-3.CrossRefPubMedGoogle Scholar
  4. 4.
    Grant CS. Insulinoma. Best Pract Res Clin Gastroenterol. 2005;19:783–98. doi:10.1016/j.bpg.2005.05.008.CrossRefPubMedGoogle Scholar
  5. 5.
    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.CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Kaltsas GA, Besser GM, Grossman AB. The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev. 2004;25:458–511.CrossRefPubMedGoogle Scholar
  7. 7.
    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.CrossRefPubMedGoogle Scholar
  8. 8.
    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.Google Scholar
  9. 9.
    Christ E, Wild D, Forrer F, Brandle M, Sahli R, Clerici T, et al. Glucagon-like peptide-1 receptor imaging for localization of insulinomas. J Clin Endocrinol Metab. 2009;94:4398–405. doi:10.1210/jc.2009-1082.CrossRefPubMedGoogle Scholar
  10. 10.
    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.CrossRefPubMedGoogle Scholar
  11. 11.
    Brom M, Oyen WJ, Joosten L, Gotthardt M, Boerman OC. 68Ga-labelled exendin-3, a new agent for the detection of insulinomas with PET. Eur J Nucl Med Mol Imaging. 2010;37:1345–55. doi:10.1007/s00259-009-1363-y.CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    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.CrossRefPubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedGoogle Scholar
  14. 14.
    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.CrossRefPubMedGoogle Scholar
  15. 15.
    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.CrossRefPubMedGoogle Scholar
  16. 16.
    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.CrossRefPubMedGoogle Scholar
  17. 17.
    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.CrossRefPubMedGoogle Scholar
  18. 18.
    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.CrossRefPubMedGoogle Scholar
  19. 19.
    Kauhanen S, Seppanen M, Minn H, Nuutila P. Clinical PET imaging of insulinoma and beta-cell hyperplasia. Curr Pharm Des. 2010;16:1550–60.CrossRefPubMedGoogle Scholar
  20. 20.
    Hoegerle S, Altehoefer C, Ghanem N, Koehler G, Waller CF, Scheruebl H, et al. Whole-body 18F dopa PET for detection of gastrointestinal carcinoid tumors. Radiology. 2001;220:373–80. doi:10.1148/radiology.220.2.r01au25373.CrossRefPubMedGoogle Scholar
  21. 21.
    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.CrossRefPubMedGoogle Scholar
  22. 22.
    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.CrossRefPubMedGoogle Scholar
  23. 23.
    Koopmans KP, de Vries EG, Kema IP, Elsinga PH, Neels OC, Sluiter WJ, et al. Staging of carcinoid tumours with 18F-DOPA PET: a prospective, diagnostic accuracy study. Lancet Oncol. 2006;7:728–34. doi:10.1016/S1470-2045(06)70801-4.CrossRefPubMedGoogle Scholar
  24. 24.
    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.CrossRefPubMedGoogle Scholar
  25. 25.
    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.CrossRefPubMedGoogle Scholar
  26. 26.
    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.CrossRefPubMedGoogle Scholar
  27. 27.
    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.CrossRefPubMedGoogle Scholar
  28. 28.
    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.CrossRefPubMedGoogle Scholar
  29. 29.
    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.PubMedGoogle Scholar
  30. 30.
    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.CrossRefPubMedGoogle Scholar
  31. 31.
    Treglia G, Inzani F, Campanini N, Rindi G, Agnes S, Giordano A, et al. A case of insulinoma detected by 68Ga-DOTANOC PET/CT and missed by 18F-dihydroxyphenylalanine PET/CT. Clin Nucl Med. 2013;38:e267–70. doi:10.1097/RLU.0b013e31825b222f.CrossRefPubMedGoogle Scholar
  32. 32.
    Wild D, Christ E, Caplin ME, Kurzawinski TR, Forrer F, Brandle M, et al. Glucagon-like peptide-1 versus somatostatin receptor targeting reveals 2 distinct forms of malignant insulinomas. J Nucl Med. 2011;52:1073–8. doi:10.2967/jnumed.110.085142.CrossRefPubMedGoogle Scholar
  33. 33.
    Soussan M, Nataf V, Kerrou K, Grahek D, Pascal O, Talbot JN, et al. Added value of early 18F-FDOPA PET/CT acquisition time in medullary thyroid cancer. Nucl Med Commun. 2012;33:775–9. doi:10.1097/MNM.0b013e3283543304.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Alessio Imperiale
    • 1
    • 2
  • Frédéric Sebag
    • 3
  • Michel Vix
    • 4
  • Frédéric Castinetti
    • 5
  • Laurence Kessler
    • 6
  • François Moreau
    • 6
  • Philippe Bachellier
    • 7
  • Benjamin Guillet
    • 8
  • Izzie-Jacques Namer
    • 1
    • 2
  • Olivier Mundler
    • 8
  • David Taïeb
    • 8
    • 9
  1. 1.Department of Biophysics and Nuclear MedicineUniversity Hospitals of StrasbourgStrasbourgFrance
  2. 2.Faculty of Medicine, ICube - UMR 7357University of Strasbourg/CNRS and FMTSStrasbourgFrance
  3. 3.Department of Endocrine Surgery, La Timone University HospitalAix-Marseille UniversityMarseilleFrance
  4. 4.Department of General, Digestive, and Endocrine Surgery, IRCAD-IHUUniversity of StrasbourgStrasbourgFrance
  5. 5.Department of Endocrinology, Diabetes and Metabolic Disorders, La Timone University HospitalAix-Marseille UniversityMarseilleFrance
  6. 6.Department of Diabetology, University Hospital of StrasbourgUniversity of StrasbourgStrasbourgFrance
  7. 7.Department of Visceral Surgery and TransplantationUniversity Hospitals of StrasbourgStrasbourgFrance
  8. 8.Department of Nuclear Medicine, La Timone University Hospital, CERIMEDAix-Marseille UniversityMarseilleFrance
  9. 9.Biophysics and Nuclear Medecine, La Timone University Hospital, European Center for Research in Medical ImagingAix-Marseille UniversityMarseilleFrance

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