Comparison of glucagon-like peptide-1 receptor (GLP-1R) PET/CT, SPECT/CT and 3T MRI for the localisation of occult insulinomas: evaluation of diagnostic accuracy in a prospective crossover imaging study

  • Kwadwo Antwi
  • Melpomeni Fani
  • Tobias Heye
  • Guillaume Nicolas
  • Christof Rottenburger
  • Felix Kaul
  • Elmar Merkle
  • Christoph J. Zech
  • Daniel Boll
  • Deborah R. Vogt
  • Beat Gloor
  • Emanuel Christ
  • Damian Wild
Original Article



Benign insulinomas are the most prevalent cause of endogenous hyperinsulinaemic hypoglycaemia (EHH) in adults, and because of their small size are difficult to localise. The purpose of the study was to test the diagnostic accuracy and clinical impact of glucagon-like peptide-1 receptor (GLP-1R) PET/CT using 68Ga-DOTA-exendin-4 in consecutive adult patients referred for localisation of insulinomas. The results were compared with 111In-DOTA-exendin-4 SPECT/CT, study-MRI and previously performed external CT and/or MRI (prior external CT/MRI).


We prospectively enrolled patients with neuroglycopenic symptoms due to EHH. GLP-1R PET/CT, SPECT/CT and study-MRI were performed in a randomised, crossover order within 3–4 days. The reference standard was surgery with histology and treatment outcome.


From January 2014 until March 2017, 52 patients were recruited. All imaging and invasive procedures before recruitment identified suspicious lesions in 46.2% of patients. GLP-1R PET/CT, SPECT/CT and study-MRI detected suspicious lesions in 78.8%, 63.5% and 63.4% of patients, respectively. In 38 patients, conclusive histology was available for final analysis.

Accuracy (95% confidence interval) for PET/CT, SPECT/CT, study-MRI and prior external CT/MRI was 93.9% (87.8–97.5%), 67.5% (58.1–76.0%), 67.6% (58.0–76.1%) and 40.0% (23.9–57.9%), respectively (all P values < 0.01, except comparison of SPECT/CT and study-MRI with a P value = 1.0). Impact on clinical management was 42.3%, 32.7% and 33.3% for PET/CT, SPECT/CT and study-MRI, respectively. Percentage reading agreement was 89.5%, 75.7%, and 71.1% for PET/CT, SPECT/CT and study-MRI, respectively.


68Ga-DOTA-exendin-4 PET/CT performed significantly better than 111In-DOTA-exendin-4 SPECT/CT and MRI in the localisation of benign insulinomas and should be considered in patients where localisation fails with CT/MRI (, NCT02127541).


Insulinoma Glucagon-like peptide-1 receptor GLP-1R PET/CT GLP-1R SPECT/CT MRI 68Ga-DOTA-exendin-4 



We thank all the patients who participated in the trial, the referring physicians and the local investigators who contributed to the trial, and the technicians who did the labelling and the scans. We especially thank Prof. Aurel Perren, Institute of Pathology, University Bern, Switzerland, for pathological review, and Astrid Roesler, Clinical Trial Unit, Department of Clinical Research, University Hospital Basel and University of Basel, Switzerland, for monitoring the study.


The study was supported by the Swiss National Science Foundation (grant number 320030-152938) and the Desirée and Niels Yde Foundation (grant number 389-12), which had no role in the study design, data collection, analysis, interpretation, or writing of the report.

Compliance with ethical standards

Disclosure of potential conflict of interest

The authors declare that they have no conflict of interest relevant to this article.

Ethical approval

The study was approved by the regional scientific ethics committee, and all procedures performed in studies involving human participants were in accordance with the ethical standards of the regional scientific ethics committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

259_2018_4101_MOESM1_ESM.docx (749 kb)
ESM 1 (DOCX 748 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kwadwo Antwi
    • 1
  • Melpomeni Fani
    • 1
  • Tobias Heye
    • 1
  • Guillaume Nicolas
    • 1
    • 2
  • Christof Rottenburger
    • 1
    • 2
  • Felix Kaul
    • 1
    • 2
  • Elmar Merkle
    • 1
  • Christoph J. Zech
    • 1
  • Daniel Boll
    • 1
  • Deborah R. Vogt
    • 3
  • Beat Gloor
    • 4
  • Emanuel Christ
    • 2
    • 5
  • Damian Wild
    • 1
    • 2
  1. 1.Clinic of Radiology and Nuclear MedicineUniversity Hospital BaselBaselSwitzerland
  2. 2.Centre for Neuroendocrine and Endocrine TumoursUniversity Hospital BaselBaselSwitzerland
  3. 3.Clinical Trial Unit, Department of Clinical ResearchUniversity Hospital Basel and University of BaselBaselSwitzerland
  4. 4.Department of Visceral SurgeryUniversity Hospital of BernBernSwitzerland
  5. 5.Division of Endocrinology, Diabetology and MetabolismUniversity Hospital BaselBaselSwitzerland

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