Skip to main content

Advertisement

Log in

Role of 68Ga somatostatin receptor PET/CT in the detection of endogenous hyperinsulinaemic focus: an explorative study

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To explore the role of 68Ga-DOTATATE/DOTATOC PET/CT (SR PET/CT) in patients with suspicion of or histopathologically proven pancreatogenic hyperinsulinaemic hypoglycaemia.

Methods

We included 13 patients with histopathologically proven or a high clinical suspicion of pancreatogenic hyperinsulinaemia. All the patients underwent a SR PET/CT scan. The results were correlated with histopathological findings. Normalization of blood glucose levels after resection of the pancreatic lesion, as well as a cytological and/or pathological diagnosis of insulinoma, was considered the diagnostic gold standard for insulinoma. The diagnosis of nesidioblastosis was based on exclusion of an insulinoma and conclusive pathological examination of a segment of the pancreas. Malignant insulinoma was defined as the presence of locoregional or distant metastases.

Results

Based on histopathology, 13 patients were found to have pancreatic hyperinsulinaemia: two patients had malignant insulinoma, eight had nonmetastasized insulinoma, and three had nesidioblastosis. SR PET was positive in 11 of the 13 patients (84.6 %) with a final diagnosis of endogenous pancreatic hypoglycaemia. Histopathological staining confirmed 16 foci of hyperinsulinism (insulin positivity). SR PET detected 14 of the 16 lesions, resulting in a sensitivity of 87 %. One intrapancreatic spleen was falsely diagnosed as insulinoma focus on SR PET, resulting in positive predictive value of 93.3 %. Immunohistochemical staining of somatostatin receptor (SSR) subtype 2a was available in ten specimens: two nesidioblastosis, and seven benign and one malignant insulinoma. Eight out of the ten specimens (80 %) stained strongly to moderately positive. Seven of the eight SSR2a-positive lesions were picked up on SR PET. Based on the results of SR PET/CT, nine patients achieved complete remission of the hypoglycaemic events during follow-up.

Conclusion

This explorative study suggests that SR PET in combination with CT may play a significant role in the detection and management of patients with pancreatogenic hyperinsulinaemic hypoglycaemia. A large proportion of insulinomas express SSR2a, and a larger study is needed to fully assess the diagnostic accuracy of SR PET in patients with insulinoma and nesidioblastosis compared with current localizing studies used in clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Grant CS. Insulinoma. Best Pract Res Clin Gastroenterol. 2005;19:783–98.

    Article  CAS  PubMed  Google Scholar 

  2. de Herder WW. Insulinoma. Neuroendocrinology. 2004;80 Suppl 1:20–2.

    Article  PubMed  Google Scholar 

  3. Klöppel G, Perren A, Heitz PU. The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci. 2004;1014:13–27.

    Article  PubMed  Google Scholar 

  4. Ferrone CR, Tang LH, Tomlinson J, Gonen M, Hochwald SN, Brennan MF, et al. Determining prognosis in patients with pancreatic endocrine neoplasms: can the WHO classification system be simplified? J Clin Oncol. 2007;25(35):5609–15.

    Article  PubMed  Google Scholar 

  5. Service FJ. Hypoglycemic disorders. N Engl J Med. 1995;332:1144–52.

    Article  CAS  PubMed  Google Scholar 

  6. Service FJ. Insulinoma and other islet-cell tumors. Cancer Treat Res. 1997;89:335–46.

    Article  CAS  PubMed  Google Scholar 

  7. Kenney B, Tormey CA, Qin L, Sosa JA, Jain D, Neto A. Adult nesidioblastosis. Clinicopathologic correlation between pre-operative selective arterial calcium stimulation studies and post-operative pathologic findings. JOP. 2008;9:504–11.

    PubMed  Google Scholar 

  8. Jensen RT, Cadiot G, Brandi ML, de Herder WW, Kaltsas G, Komminoth P, et al. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology. 2012;95:98–119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Noone TC, Hosey J, Firat Z, Semelka RC. Imaging and localization of islet-cell tumours of the pancreas on CT and MRI. Best Pract Res Clin Endocrinol Metab. 2005;19:195–211.

    Article  PubMed  Google Scholar 

  10. Gouya H, Vignaux O, Augui J, Dousset B, Palazzo L, Louvel A, et al. CT, endoscopic sonography, and a combined protocol for preoperative evaluation of pancreatic insulinomas. AJR Am J Roentgenol. 2003;181:987–92.

    Article  PubMed  Google Scholar 

  11. Pamuklar E, Semelka RC. MR imaging of the pancreas. Magn Reson Imaging Clin N Am. 2005;13:313–30.

    Article  PubMed  Google Scholar 

  12. McLean AM, Fairclough PD. Endoscopic ultrasound in the localisation of pancreatic islet cell tumours. Best Pract Res Clin Endocrinol Metab. 2005;19:177–93.

    Article  CAS  PubMed  Google Scholar 

  13. de Herder WW, Kwekkeboom DJ, Valkema R, Feelders RA, van Aken MO, Lamberts SW, et al. Neuroendocrine tumors and somatostatin: imaging techniques. J Endocrinol Invest. 2005;28(11 Suppl International):132–6.

    PubMed  Google Scholar 

  14. Vezzosi D, Bennet A, Rochaix P, Courbon F, Selves J, Pradere B, et al. Octreotide in insulinoma patients: efficacy on hypoglycemia, relationships with Octreoscan scintigraphy and immunostaining with anti-sst2A and anti-sst5 antibodies. Eur J Endocrinol. 2005;152(5):757–67.

    Article  CAS  PubMed  Google Scholar 

  15. de Sá SV, Corrêa-Giannella ML, Machado MC. Somatostatin receptor subtype 5 (SSTR5) mRNA expression is related to histopathological features of cell proliferation in insulinomas. Endocr Relat Cancer. 2006;13(1):69–78.

    Article  PubMed  Google Scholar 

  16. Kaemmerer D, Peter L, Lupp A, Schulz S, Sänger J, Prasad V, Kulkarni H, et al. Molecular imaging with 68Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011;38(9):1659–68.

  17. Bodei L, Sundin A, Kidd M, Prasad V, Modlin IM. The status of neuroendocrine tumor imaging: from darkness to light? Neuroendocrinology. 2015;101:1–17.

    Article  CAS  PubMed  Google Scholar 

  18. Rufini V, Baum RP, Castaldi P, Treglia G, De Gaetano AM, Carreras C, et al. Role of PET/CT in the functional imaging of endocrine pancreatic tumors. Abdom Imaging. 2012;37:1004–20.

    Article  PubMed  Google Scholar 

  19. Hörsch D, Kulkarni HR, Baum RP. THERANOSTICS – clinical aimshots in surgical warfare against well-differentiated neuroendocrine neoplasms. Ann Transl Med. 2014;2(1):1.

    PubMed  PubMed Central  Google Scholar 

  20. Ruf J, Schiefer J, Furth C, Kosiek O, Kropf S, Heuck F, et al. 68Ga-DOTATOC PET/CT of neuroendocrine tumors: spotlight on the CT phases of a triple-phase protocol. J Nucl Med. 2011;52(5):697–704.

    Article  PubMed  Google Scholar 

  21. Volante M, Brizzi MP, Faggiano A, La Rosa S, Rapa I, Ferrero A, et al. Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol. 2007;20(11):1172–82.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. Virgolini I, Ambrosini V, Bomanji JB, Baum RP, Fanti S, Gabriel M, et al. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE. Eur J Nucl Med Mol Imaging. 2010;37:2004–10.

  24. Antunes P, Ginj M, Zhang H, Waser B, Baum RP, Reubi JC, et al. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals? Eur J Nucl Med Mol Imaging. 2007;34(7):982–93.

    Article  CAS  PubMed  Google Scholar 

  25. Portela-Gomes GM, Stridsberg M, Grimelius L, Rorstad O, Janson ET. Differential expression of the five somatostatin receptor subtypes in human benign and malignant insulinomas – predominance of receptor subtype 4. Endocr Pathol. 2007;18(2):79–85.

    Article  CAS  PubMed  Google Scholar 

  26. 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 localization of clinically and biochemically suspected insulinoma. Q J Nucl Med Mol Imaging. 2016;60:69–76.

    PubMed  Google Scholar 

  27. Prasad V, Baum RP. Biodistribution of the Ga-68 labeled somatostatin analogue DOTA-NOC in patients with neuroendocrine tumors: characterization of uptake in normal organs and tumor lesions. Q J Nucl Med Mol Imaging. 2010;54(1):61–7.

    CAS  PubMed  Google Scholar 

  28. Service FJ, Natt N, Thompson GB, Grant CS, van Heerden JA, Andrews JC, et al. Noninsulinoma pancreatogenous hypoglycemia: a novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genes. J Clin Endocrinol Metab. 1999;84(5):1582–9.

    CAS  PubMed  Google Scholar 

  29. Thompson GB, Service FJ, Andrews JC, Lloyd RV, Natt N, van Heerden JA, et al. Noninsulinoma pancreatogenous hypoglycemia syndrome: an update in 10 surgically treated patients. Surgery. 2000;128(6):937–44.

    Article  CAS  PubMed  Google Scholar 

  30. Anlauf M, Wieben D, Perren A, Sipos B, Komminoth P, Raffel A, et al. Persistent hyperinsulinemic hypoglycemia in 15 adults with diffuse nesidioblastosis: diagnostic criteria, incidence, and characterization of beta-cell changes. Am J Surg Pathol. 2005;29(4):524–33.

    Article  PubMed  Google Scholar 

  31. Laidlaw GF. Nesidioblastoma, the islet tumor of the pancreas. Am J Pathol. 1938;14:125–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Ferrario C, Stoll D, Boubaker A, Matter M, Yan P, Puder JJ. Diffuse nesidioblastosis with hypoglycemia mimicking an insulinoma: a case report. J Med Case Rep. 2012;6:332. doi:10.1186/1752-1947-6-332.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Francesconi AB, Matos M, Lee JC, Wyld DK, Clouston AD, Macfarlane D. Nesidioblastosis as a cause of focal pancreatic 111In-pentetreotide uptake in a patient with putative VIPoma: another differential diagnosis. Ann Nucl Med. 2009;23(5):497–9.

    Article  PubMed  Google Scholar 

  34. Wild D, Behe M, Wicki A, Storch D, Waser B, Gotthardt M, et al. [Lys40(Ahx-DTPA-111In)NH2]exendin-4, a very promising ligand for glucagon-like peptide-1 (GLP-1) receptor targeting. J Nucl Med. 2006;47:2025–33.

  35. Wild D, Macke H, Christ E, Gloor B, Reubi JC. Glucagonlike peptide-1 receptor scans to localize occult insulinomas. N Engl J Med. 2008;359:766–8.

    Article  CAS  PubMed  Google Scholar 

  36. Christ E, Wild D, Forrer F, Brändle 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.

    Article  CAS  PubMed  Google Scholar 

  37. Wild D, Christ E, Caplin ME, Kurzawinski TR, Forrer F, Brändle 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.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vikas Prasad.

Ethics declarations

Funding

None.

Conflicts of interest

None.

Ethical approval

This retrospective analysis was performed in accordance with the ethical standards of the institutional research committee and with the principles of the1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Prasad, V., Sainz-Esteban, A., Arsenic, R. et al. Role of 68Ga somatostatin receptor PET/CT in the detection of endogenous hyperinsulinaemic focus: an explorative study. Eur J Nucl Med Mol Imaging 43, 1593–1600 (2016). https://doi.org/10.1007/s00259-016-3331-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-016-3331-7

Keywords

Navigation