A novel PET scan using a radioactively labeled version of the GLP-1 peptide exendin-4 detected insulinomas in all 12 patients, outperforming CT, MRI, and other conventional imaging methods.
100% detection rate18F-exendin-4 PET/CT found insulinomas in all 12 patients, compared to 63–90% for conventional imaging methods
What the researchers found
18F-exendin-4 PET/CT achieved 100% sensitivity for insulinoma detection in 12 patients, significantly outperforming CT (83%), MRI (63%), endoscopic ultrasonography (90%), and selective arterial calcium stimulation (89%). The peptide-based probe showed significantly higher uptake in tumor tissue than surrounding pancreatic tissue. All 12 lesions were surgically confirmed as insulinomas, and all patients achieved complete resolution of hypoglycemia after resection.
Why it matters
Insulinomas can be life-threatening but curable with surgery — if they can be located. Current imaging misses up to 37% of cases (MRI) or requires invasive procedures. This GLP-1 peptide-based imaging probe offers a noninvasive, highly sensitive alternative that could become the gold standard for preoperative insulinoma localization.
The numbers in context
n=12 · 100% sensitivity (18F-exendin-4 PET/CT) · CT: 83% · MRI: 63% · endoscopic ultrasound: 90% · selective arterial calcium stimulation: 89% · scans at 60 and 120 min post-injection · all lesions surgically confirmed
How the study worked
Prospective single-center phase 2 clinical trial. Twelve patients with biochemically confirmed hyperinsulinemic hypoglycemia underwent 18F-exendin-4 PET/CT with scans at 60 and 120 minutes post-injection. Results were compared to conventional imaging (CT, MRI, endoscopic ultrasound, selective arterial calcium stimulation) and verified by surgical pathology.
Who was studied
12 patients with biochemically confirmed hyperinsulinemic hypoglycemia suggestive of insulinoma at a single center
What this study cannot tell us
Very small sample of only 12 patients from a single center. As an interim report from an ongoing phase 2 trial, the final results may differ. The 100% sensitivity in such a small cohort may not hold in larger populations. Specificity data (false positive rate) was not explicitly reported.
How to read the evidence
Prospective phase 2 clinical trial with surgical pathology verification. While the design is strong, the very small sample size (n=12) and single-center setting limit the generalizability. This is an interim report from an ongoing trial.
When this study was published
Published in 2025, this is a cutting-edge phase 2 trial result using the latest generation of peptide-based PET imaging technology. The findings are highly current and clinically relevant.
The bigger picture
This represents a new diagnostic application for GLP-1 receptor-targeting peptides. Exendin-4, originally developed as a diabetes treatment (exenatide/Byetta), is repurposed here as a molecular imaging probe that exploits the overexpression of GLP-1 receptors on insulinoma cells. The success of peptide-based targeted imaging could extend to other GLP-1 receptor-expressing tumors.
Questions still open
- Will the 100% sensitivity hold in the full phase 2 trial with a larger patient cohort?
- Could 18F-exendin-4 PET/CT also detect other GLP-1 receptor-expressing neuroendocrine tumors beyond insulinomas?
- How does the cost and radiation exposure of this peptide PET scan compare to existing diagnostic approaches?
Common questions
What is exendin-4 and how is it used for imaging?
Why is finding insulinomas so difficult with regular imaging?
Read the original research
Qualitative and Quantitative Analyses of Noninvasive Diagnosis of Insulinoma Using [18F]FB(ePEG12)12-Exendin-4 PET/CT.
The Journal of clinical endocrinology and metabolism, 111(1), 209-217
Citation
Murakami, Takaaki; Yoshida, Hayao; Sakaki, Kentaro; Otani, Daisuke; Kawai Miyake, Kanae; Shimizu, Yoichi; Fujimoto, Hiroyuki; Yabe, Daisuke; Nakamoto, Yuji; Inagaki, Nobuya. (2025). Qualitative and Quantitative Analyses of Noninvasive Diagnosis of Insulinoma Using [18F]FB(ePEG12)12-Exendin-4 PET/CT.. The Journal of clinical endocrinology and metabolism, 111(1), 209-217. https://doi.org/10.1210/clinem/dgaf253