Glucagon-Like Peptide-1 Receptor PET/CT with 68Ga-NOTA-Exendin-4 for Detecting Localized Insulinoma: A Prospective Cohort Study

Preoperative localization of insulinoma is a clinical dilemma. We aimed to investigate whether glucagon-like peptide-1 receptor (GLP-1R) PET/CT with Ga-68-NOTA-MAL-cys(40)-exendin-4 (Ga-68-NOTA-exendin-4) is efficient in detecting insulinoma. Methods: In our prospective cohort study, patients with endogenous hyperinsulinemic hypoglycemia were enrolled. CT, MRI, endoscopic ultrasound, and Tc-99m-hydrazinonicotinamide-TOC SPECT/CT were done according to standard protocols. GLP-1R PET/CT was performed 30-60 min after the injection of Ga-68-NOTA-exendin-4. The gold standard for diagnosis was the histopathologic results after surgery. Results: Of 52 recruited patients, 43 patients with histopathologically proven insulinomas were included for the imaging studies. Nine patients did not undergo surgical intervention. Ga-68-NOTA-exendin-4 PET/CT correctly detected insulinomas in 42 of 43 patients with high tumor uptake (mean SUVavg +/- SD, 10.2 +/- 4.9; mean SUVmax +/- SD, 23.6 +/- 11.7), resulting in sensitivity of 97.7%. In contrast, Tc-99m-hydrazinonicotinamide-TOC SPECT/CT showed a low sensitivity of 19.5% (8/41) in this group of patients; however, it successfully localized the tumor that was false negative with GLP-1R PET/CT. The sensitivities of CT, MR, and endoscopic ultrasonography were 74.4% (32/43), 56.0% (14/25), and 84.0% (21/25), respectively. Conclusion: 68Ga-NOTA-exendin-4 PET/CT is a highly sensitive imaging technique for the localization of insulinoma.