Ga-DOTA-exendin-4 PET/CT performed significantly better than In-DOTA-exendin-4 SPECT/CT and MRI in the localisation of benign insulinomas and should be considered in patients where localisation fails with CT/MRI ( ClinicalTrials.gov , NCT02127541).

111 In-DOTA-exendin-4 SPECT/CT has been shown to be highly efficient in the detection of insulinomas. We aimed at determining whether novel PET/CT imaging with [Nle 14 ,Lys 40 (Ahx-DOTA-68 Ga) NH 2 ]exendin-4 ( 68 Ga-DOTA-exendin-4) is feasible and sensitive in detecting benign insulinomas. Methods: 68 Ga-DOTA-exendin-4 PET/CT and 111 In-DOTA-exendin-4 SPECT/CT were performed in a randomized cross-over order on 5 patients with endogenous hyperinsulinemic hypoglycemia. The gold standard for comparison was the histologic diagnosis after surgery. Results: In 4 patients histologic diagnosis confirmed a benign insulinoma, whereas one patient refused surgery despite a positive 68 Ga-DOTA-exendin-4 PET/CT scan. In 4 of 5 patients, previously performed conventional imaging (CT or MR imaging) was not able to localize the insulinoma. 68 Ga-DOTA-exendin-4 PET/CT correctly identified the insulinoma in 4 of 4 patients, whereas 111 In-DOTA-exendin-4 SPECT/CT correctly identified the insulinoma in only 2 of 4 patients. Conclusion: These preliminary data suggest that the use of 68 Ga-DOTA-exendin-4 PET/CT in detecting hidden insulinomas is feasible.

Receptors for the incretin glucagon-like peptide-1 (GLP-1R) have been found overexpressed in selected types of human tumors and may, therefore, play an increasingly important role in endocrine gastrointestinal tumor management. In particular, virtually all benign insulinomas express GLP-1R in high density. Targeting GLP-1R with indium-111, technetium-99m or gallium-68-labeled exendin-4 offers a new approach that permits the successful localization of small benign insulinomas. It is likely that this new non-invasive technique has the potential to replace the invasive localization of insulinomas by selective arterial stimulation and venous sampling. In contrast to benign insulinomas, malignant insulin-secreting neuroendocrine tumors express GLP-1R in only one-third of the cases, while they more often express the somatostatin subtype 2 receptors. Importantly, one of the two receptors appears to be always overexpressed. In special cases of endogenous hyperinsulinemic hypoglycemia (EHH), that is, in the context of MEN-1 or adult nesidioblastosis GLP-1R imaging is useful whereas in postprandial hypoglycemia in the context of bariatric surgery, GLP-1R imaging is probably not helpful. This review focuses on the potential use of GLP-1R imaging in the differential diagnosis of EHH.

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