68Ga-Exendin-4 PET/CT Detects Insulinomas in Patients With Endogenous Hyperinsulinemic Hypoglycemia in MEN-1

J Clin Endocrinol Metab. 2019 Dec 1;104(12):5843-5852. doi: 10.1210/jc.2018-02754.


Context: Surgical intervention is advised in patients with multiple endocrine neoplasia type-1 (MEN-1) and nonfunctioning pancreatic neuroendocrine tumors (PanNETs) with a size ≥20 mm. Functioning PanNETs, such as in patients with endogenous hyperinsulinemic hypoglycemia (EHH) due to (one or multiple) insulinomas, should be treated surgically independent of size. Preoperative localization of insulinomas is critical for surgery.

Objective: To evaluate the feasibility and sensitivity of 68Ga-DOTA-exendin-4 positron emission tomography (PET)/CT in the detection of clinically relevant lesions in patients with MEN-1 and EHH in combination with MRI.

Design: Post hoc subgroup analysis of a larger prospective imaging study with 52 patients with EHH.

Patients: Six of 52 consecutive patients with EHH and genetically proven MEN-1 mutation were included.

Interventions: All patients received one 68Ga-DOTA-exendin-4 PET/CT and one MRI scan within 3 to 4 days. Thereafter, surgery was performed based on all imaging results.

Main outcome measures: Lesion-based sensitivity of PET/CT and MRI for detection of clinically relevant lesions was calculated. Readers were unaware of other results. The reference standard was surgery with histology and treatment outcome. True positive (i.e., clinically relevant lesions) was defined as PanNETs ≥20 mm or insulinoma.

Results: In six patients, 37 PanNETs were confirmed by histopathology. Sensitivity (95% CI) in the detection of clinically relevant lesions for combined PET/CT plus MRI, MRI, and PET/CT was 92.3% (64% to 99.8%), 38.5% (13.9% to 68.4%), and 84.6% (54.6% to 98.1%), respectively (P = 0.014 for the comparison of PET/CT plus MRI vs MRI). Postsurgery, EHH resolved in all patients.

Conclusion: 68Ga-DOTA-exendin-4 PET/CT is feasible in patients with MEN-1 and EHH. The combination with MRI is superior to MRI alone in the detection of insulinomas and may guide the surgical strategy.

Trial registration: ClinicalTrials.gov NCT02127541.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Congenital Hyperinsulinism / complications*
  • Congenital Hyperinsulinism / genetics
  • Feasibility Studies
  • Female
  • Humans
  • Insulinoma / diagnostic imaging*
  • Insulinoma / genetics
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 1 / complications*
  • Multiple Endocrine Neoplasia Type 1 / genetics
  • Organometallic Compounds*
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / genetics
  • Peptides*
  • Positron Emission Tomography Computed Tomography*
  • Prospective Studies
  • Sensitivity and Specificity
  • Young Adult


  • 68Ga-DOTA-exendin-4
  • Organometallic Compounds
  • Peptides

Associated data

  • ClinicalTrials.gov/NCT02127541