68Ga-DOTA-exendin-4 PET/CT for Insulinoma Localization in Patients with Negative or Inconclusive Conventional Imaging

CONTEXT: Insulinomas are the main cause of endogenous hyperinsulinemic hypoglycemia (EHH) in adults, with surgery as the only cure. Pancreas-preserving surgery is preferred, making precise preoperative localization crucial. GLP-1R-targeted imaging, such as [68Ga]Ga-DOTA-exendin-4 PET/CT, outperforms other imaging procedures for insulinoma localization. OBJECTIVE: To investigate the performance and clinical impact of [68Ga]Ga-DOTA-exendin-4 PET/CT for the detection of insulinomas in patients with EHH and prior negative or inconclusive conventional imaging. METHODS: In this retrospective, real-world, dual-center imaging study, 101 patients with biochemically proven EHH and/or a positive Whipple's triad underwent [68Ga]Ga-DOTA-exendin-4 PET/CT at two tertiary centers between April 2017 and March 2024. Among these, 58 patients with prior negative or inconclusive conventional imaging constituted the primary analysis cohort. Endpoints: Insulinoma detection rate and sensitivity by [68Ga]Ga-DOTA-exendin-4 PET/CT after negative or inconclusive conventional imaging and impact on clinical management. RESULTS: Among the 58 patients with prior negative or inconclusive conventional imaging, [68Ga]Ga-DOTA-exendin-4 PET/CT was positive in 42 patients, corresponding to a detection rate of 72% (95% CI, 59-83%). Thirty patients subsequently underwent PET/CT-guided surgery. Overall, 32 patients had histological verification (including two PET/CT-negative cases), corresponding to a sensitivity of 93.8% (95% CI, 79-99%). CONCLUSION: In real-world clinical practice, [68Ga]Ga-DOTA-exendin-4 PET/CT provides a high detection rate of 72% for localizing insulinomas, including one case of diffuse nesidioblastosis in patients with EHH and prior negative or inconclusive conventional imaging, thereby enabling PET/CT-guided surgical approaches. These findings underscore the substantial clinical impact of GLP-1R-targeted PET/CT on patient management and prognosis.GLP-1 receptor.