Improved Localization of Insulinomas Using 68Ga-NODAGA-Exendin-4 PET/CT

Abstract

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.

Keywords: GLP-1 receptor; diagnostic imaging; exendin PET/CT; insulinoma.

Graphical abstract

FIGURE 1.

Insulinoma-to-background ratio and contrast-to-noise ratio of exendin PET/CT and DOTA-SSA PET/CT images. *P < 0.05.

FIGURE 2.

(A) Exendin PET/CT and DOTA-SSA PET/CT images of patient 56, with highest insulinoma-to-background ratio in exendin PET (31.5 vs. 2.3 in DOTA-SSA PET). Images of patients 4 (B) and 17 (C) show intermediate insulinoma-to-background ratios in exendin PET (8.9 and 10.4, respectively, vs. 2.2 and 2.3 in DOTA-SSA PET, respectively). (D) Images of patient 26 have lowest insulinoma-to-background ratio in exendin PET (7.3 vs. 12.2 in DOTA-SSA PET), showing still excellent visibility of insulinoma. Location of insulinomas is indicated with arrows.

FIGURE 3.

Images of exendin PET/CT, DOTA-SSA-PET/CT, and CE-DWI-MRI (T1-weighted precontrast) of patient 8. Location of insulinoma in pancreas body is indicated with arrows. Only exendin PET/CT was true positive in this patient.