Comparison of PET/CT using ⁶⁸Ga-NOTA-Exendin-4 with ⁶⁸Ga-DOTATATE, ¹⁸F-FDG, and conventional imaging in the localization of insulinomas.

PURPOSE: Accurate preoperative localization is particularly important for surgical treatment of insulinomas. Current imaging methods, including F-FDG (FDG) PET/CT, Ga-DOTATATE (TATE) PET/CT, CE-CT, and CE-MRI, have limitations. This prospective study provides a direct comparison of Ga-NOTA-Exendin-4 (Ex4) PET/CT with other imaging techniques. METHOD: 47 patients with biochemically proven endogenous hyperinsulinemic hypoglycemia underwent Ex4 PET/CT and other imaging methods. Sensitivity and accuracy of all imaging procedures for localizing insulinoma were calculated at the patient level and lesion level. Both clinical (>10 years experience) and junior (< 2 years experience) nuclear medicine physician readings were used to assess the diagnostic efficacy. We compared the SUV and tumor-to-background ratio (TBR) of three tracers and analyzed the values with Ki-67, maximum tumor diameter, and glucose metabolism indicators. RESULTS: In patient level, the sensitivity and accuracy of Ex4 PET/CT (94.11% and 95.74%) were higher than TATE PET/CT (70.59%, p = 0.026; 78.72%, p = 0.030), FDG PET/CT (50.00%, p < 0.001; 63.83%, p < 0.001), CE-CT (77.77%, p = 0.135; 72.22%, p = 0.007), and CE-MRI (63.64%, p = 0.135; 43.75%, p < 0.001), respectively. Interobserver agreement was higher for Ex4 PET/CT than TATE PET/CT and FDG PET/CT (Cohen κ, 0.839 vs. 0.707 and 0.784, respectively). SUV and TBR of Ex4 and TATE PET/CT were significantly higher than FDG PET/CT (p < 0.01). Negative correlations of tumor Ki-67 with TATE PET/CT were observed with SUV (r = -0.637, p < 0.001). SUV and TBR of three molecular imaging methods had positive correlations with the maximum tumor diameter (p < 0.05), except TBR of FDG PET/CT. Semi-quantitative values of the three tracers showed no correlation with the lowest blood glucose level, corresponding insulin, and C-peptide level. TBR of TATE PET/CT showed a positive correlation with C-peptide (r = 0.393, p = 0.043). CONCLUSION: Ex4 PET/CT showed superior characteristics in localization compared to routine imaging modalities in benign insulinomas. Ex4 PET/CT demonstrates better imaging quality and interpretability than FDG PET/CT and TATE PET/CT. Combined Ex4 and TATE PET/CT could provide a comprehensive evaluation/localization of insulinoma. TRIAL REGISTRATION: The trial was retrospectively registered at ClinitalTrial.gov (NCT06690957 and NCT06725693) on November 14, 2024 and December 5, 2024.