Imaging with radiolabeled exendin enables detection and characterization of glucagon-like peptide 1 receptors (GLP-1Rs) in vivo with high specificity. The novel radiotracer [68Ga]Ga-NODAGA-exendin-4 forms a stable complex after a simple and fast labeling procedure. Beta-cell mass in the islets of Langerhans can be visualized using [68Ga]Ga-NODAGA-exendin-4, which is promising for research into diabetes mellitus (DM) pathophysiology. Furthermore, this radiotracer enables very sensitive detection of insulinomas, resulting from vast overexpression of GLP-1Rs, and seems promising for the detection of focal lesions in congenital hyperinsulinism (CHI). Here, we describe the procedures involved in [68Ga]Ga-NODAGA-exendin-4 positron emission tomography (PET)/computed tomography (CT) imaging including the radiolabeling of the NODAGA-exendin conjugate with 68Ga, quality controls, and PET/CT.

Surgery with curative intent can be offered to Congenital Hyperinsulinism (CHI) patients, provided that the lesion is focal. Radiolabeled Exendin-4 specifically binds the glucagon-like peptide 1 receptor (GLP-1R) on pancreatic beta cells. In this study we compared the performance of [18F]F-DOPA positron emission tomography/computed tomography (DOPA PET) and PET/CT with the new tracer [68Ga]Ga-NODAGA-exendin-4 (Exendin PET) in the preoperative detection of focal CHI. Methods: Nineteen CHI patients underwent both DOPA PET and Exendin PET prior to surgery. The images were evaluated in three settings a) standard clinical reading b) blinded expert reading and c) joined reading. Target (lesion) / non target (normal pancreas) ratio were determined using maximum standard uptake value (SUVmax). Image quality was rated by pediatric surgeons in a questionnaire. Results: Fourteen/nineteen patients having focal lesions underwent surgery. Based on clinical readings, the sensitivity of Exendin PET (100% (CI 77-100%)) was higher than that of DOPA PET (71% (CI 42-92%)). Interobserver agreement between readings was higher for Exendin than for DOPA PET (Fleiss\' kappa 0.91 vs. 0.56). Exendin PET provided significantly (P = 0.021) higher target / non target ratios (2.02 ± 0.65 ) than DOPA PET (1.40 ± 0.40). On a five point scale, Pediatric surgeons rated Exendin PET superior to DOPA PET. Conclusion: Exendin PET has higher clinical sensitivity and better interobserver correlation for the detection of focal CHI than DOPA PET. Better contrast and image quality makes Exendin PET superior to DOPA PET in surgeons\' intra-operative quest for lesion localization.