An Exendin-4-based PET/CT scan detected insulinomas with 94% sensitivity and 96% accuracy, significantly outperforming all conventional and molecular imaging methods.
94.1% sensitivityThe Exendin-4 PET/CT detected insulinomas in 94.1% of patients, compared to just 50% for standard FDG-PET and 70.6% for DOTATATE PET — a transformative improvement for this challenging diagnosis.
What the researchers found
In 47 patients with biochemically proven hyperinsulinemic hypoglycemia, the peptide-based tracer 68Ga-NOTA-Exendin-4 PET/CT achieved 94.11% sensitivity and 95.74% accuracy for localizing insulinomas — significantly outperforming 68Ga-DOTATATE PET/CT (70.59% sensitivity, p=0.026), 18F-FDG PET/CT (50.00% sensitivity), and conventional imaging (CE-CT/CE-MRI).
Exendin-4 PET/CT also showed better imaging quality and easier interpretation than the other molecular imaging methods. Combining Exendin-4 and DOTATATE PET/CT could provide comprehensive evaluation of insulinomas.
Why it matters
Insulinomas are rare pancreatic tumors that cause dangerous low blood sugar. Finding them before surgery is critical but difficult — conventional imaging often misses them. This peptide-based imaging approach nearly doubles the detection rate compared to standard PET tracers, potentially transforming how these tumors are located and treated.
How the study worked
A prospective study of 47 patients with biochemically confirmed endogenous hyperinsulinemic hypoglycemia. All patients underwent 68Ga-NOTA-Exendin-4 PET/CT alongside other imaging methods (68Ga-DOTATATE PET/CT, 18F-FDG PET/CT, CE-CT, CE-MRI). Sensitivity and accuracy were calculated at both patient and lesion levels. Both experienced (>10 years) and junior radiologists interpreted the scans to assess interpretability.
Who was studied
Patients with biochemically proven endogenous hyperinsulinemic hypoglycemia (suspected insulinoma)
What this study cannot tell us
Relatively small sample of 47 patients, though insulinomas are rare. The study was retrospectively registered on ClinicalTrials.gov. 68Ga-NOTA-Exendin-4 is not yet widely available, limiting immediate clinical applicability. Results may not generalize to malignant insulinomas, as the study focused on benign tumors.
How to read the evidence
This is a prospective comparative study with head-to-head testing of multiple imaging modalities in the same patients, providing strong diagnostic accuracy evidence. However, the sample size of 47 is modest.
When this study was published
Published in 2025, this is a very recent study advancing the clinical application of peptide-based molecular imaging.
The bigger picture
This study demonstrates a powerful application of peptide science beyond therapy — using peptides as precision diagnostic tools. The GLP-1 receptor, which is the target of blockbuster weight loss drugs like semaglutide, is leveraged here for its high expression on insulinoma cells to create a molecular beacon that lights up these hard-to-find tumors on PET scans.
Questions still open
- Could Exendin-4 PET/CT become the standard first-line imaging for suspected insulinoma?
- Does this peptide-based imaging approach work for detecting malignant or metastatic insulinomas?
- Could similar GLP-1 receptor-targeted tracers be developed for other GLP-1R-expressing tumors?
Common questions
What is Exendin-4 and how does it help find insulinomas?
Why are insulinomas so hard to find with regular imaging?
Read the original research
Comparison of PET/CT using 68Ga-NOTA-Exendin-4 with 68Ga-DOTATATE, 18F-FDG, and conventional imaging in the localization of insulinomas.
European journal of nuclear medicine and molecular imaging, 52(11), 4102-4111
Citation
Yu, Haonan; Bao, Xiangyuan; Gu, Yian; Pan, Meijie; He, Qing; Li, Dong; Chen, Qiusong; Yao, Shaobo. (2025). Comparison of PET/CT using 68Ga-NOTA-Exendin-4 with 68Ga-DOTATATE, 18F-FDG, and conventional imaging in the localization of insulinomas.. European journal of nuclear medicine and molecular imaging, 52(11), 4102-4111. https://doi.org/10.1007/s00259-025-07288-x