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J Clin Endocrinol Metab. 2014 May;99(5):1519-24. doi: 10.1210/jc.2013-3541. Epub 2014 Feb 10.

Detection of metastatic insulinoma by positron emission tomography with [(68)ga]exendin-4-a case report.

Author information

Preclinical PET Platform (O.E., I.V., R.K.S.), Department of Medicinal Chemistry, Uppsala University, SE-751 83 Uppsala, Sweden; Department of Radiology, Oncology, and Radiation Sciences (I.V., L.J., G.A., J.S.), Uppsala University, SE-751 83 Uppsala, Sweden; PET Centre (I.V., G.A., J.S.), Centre for Medical Imaging, Uppsala University Hospital, Uppsala, SE-751 83 Sweden; Beckman Research Institute of the City of Hope (F.K.), Duarte, California 91010; AstraZeneca R&D (L.J.), SE-431 50 Mölndal, Sweden; Department of Medical Sciences (B.E.), Uppsala University, SE-751 83 Uppsala, Sweden; and Department of Immunology, Genetics, and Pathology (O.K.), Uppsala University SE-751 83, Uppsala, Sweden.



Insulinomas are the most common cause of endogenous hyperinsulinemic hypoglycemia in nondiabetic adult patients. They are usually benign, and curative surgery is the "gold standard" treatment if they can be localized. Malignant insulinomas are seen in less than 10% of patients, and their prognosis is poor. The glucagon like peptide-1 receptor (GLP-1R) is markedly up-regulated in insulinomas-especially benign lesions, which are difficult to localize with current imaging techniques.


The aim of the study was to assess the possibility of the detection of primary and metastatic insulinoma by positron emission tomography (PET) using [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 ([(68)Ga]Exendin-4) in a patient with severe hypoglycemia.


Dynamic and static PET/computed tomography (CT) examination of a patient was performed using [(68)Ga]Exendin-4 at Uppsala University Hospital, Uppsala, Sweden.


A patient presented with hypoglycemia requiring continuous iv glucose infusions. A pancreatic insulinoma was suspected, and an exploratory laparotomy was urgently performed. At surgery, a tumor in the pancreatic tail with an adjacent metastasis was found, and a distal pancreatic resection (plus splenectomy) and removal of lymph node were performed. Histopathology showed a World Health Organization classification grade II insulinoma. Postoperatively, hypoglycemia persisted, but a PET/CT examination using the neuroendocrine marker [(11)C]-5-hydroxy-L-tryptophan was negative.


The patient was administered [(68)Ga]Exendin-4 and was examined by dynamic PET over the liver and pancreas.


The stable GLP-1 analog Exendin-4 was labeled with (68)Ga for PET imaging of GLP-1R-expressing tumors. The patient was examined by [(68)Ga]Exendin-4-PET/CT, which confirmed several small GLP-1R-positive lesions in the liver and a lymph node that could not be conclusively identified by other imaging techniques. The results obtained from the [(68)Ga]Exendin-4-PET/CT examination provided the basis for continued systemic treatment.


The results of the [(68)Ga]Exendin-4-PET/CT examination governed the treatment strategy of this particular patient and demonstrated the potential of this technique for future management of patients with this rare but potentially fatal disease.

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