PT - JOURNAL ARTICLE AU - Boss, Marti AU - Eriksson, Olof AU - Mikkola, Kirsi AU - Eek, Annemarie AU - Brom, Maarten AU - Buitinga, Mijke AU - Brouwers, Adrienne H. AU - Velikyan, Irina AU - Waser, Beatrice AU - Kauhanen, Saila AU - Solin, Olof AU - Marciniak, Camille AU - Eriksson, Barbro AU - Reubi, Jean-Claude AU - Aveline, Cyrielle AU - Wild, Damian AU - Pattou, Francois AU - Talbot, Jean-Noel AU - Hofland, Johannes AU - Sundin, Anders AU - Nuutila, Pirjo AU - Hermans, John AU - Gotthardt, Martin TI - Improved Localization of Insulinomas Using <sup>68</sup>Ga-NODAGA-Exendin-4 PET/CT AID - 10.2967/jnumed.124.268158 DP - 2024 Oct 17 TA - Journal of Nuclear Medicine PG - jnumed.124.268158 4099 - http://jnm.snmjournals.org/content/early/2024/10/17/jnumed.124.268158.short 4100 - http://jnm.snmjournals.org/content/early/2024/10/17/jnumed.124.268158.full AB - Precise anatomic localization of insulinomas is crucial for surgical treatment. Current routine noninvasive imaging techniques, including CT, MRI, and 68Ga-DOTA-somatostatin analog (DOTA-SSA) PET/CT, have limited sensitivity. Endoscopic ultrasound is highly sensitive but invasive. In this prospective multicenter study, we compared the diagnostic accuracy of 68Ga-NODAGA-exendin-4 (exendin) PET/CT with all routine imaging procedures for the localization of insulinomas. Methods: Sixty-nine adults with biochemically proven adult endogenous hyperinsulinemic hypoglycemia underwent exendin PET/CT and current routine imaging. Images were evaluated in a clinical reading and in an expert reading. Image quality was determined by quantitative analysis. Results: Based on clinical readings, the accuracy of exendin PET/CT (94.4%; 95% CI, 84.6%–98.8%) was greater than that of DOTA-SSA PET/CT (64.8%; 95% CI, 50.6%–77.3%), contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (83.3%; 95% CI, 70.7%–92.1%), and endoscopic ultrasound (82.8%; 95% CI, 64.1%–94.1%). In 13% of patients, a correct diagnosis was only reached after exendin PET/CT. Interobserver agreement between readings was higher for exendin PET/CT than for DOTA-SSA PET/CT and contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (Cohen κ, 1.0 vs. 0.5 and 0.55). Exendin PET/CT provided a higher insulinoma-to-background ratio (15.3 ± 6.7 vs. 5.2 ± 3.0) and contrast-to-noise ratio (22.6 ± 11.1 vs. 5.1 ± 3.7) than did DOTA-SSA PET/CT. Conclusion: This study demonstrates the superiority of exendin PET/CT in a unique prospective comparison to all current routine imaging modalities for preoperative localization of benign insulinomas, providing the level of evidence needed for clinical implementation.