Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study

Lancet Diabetes Endocrinol. 2013 Oct;1(2):115-22. doi: 10.1016/S2213-8587(13)70049-4. Epub 2013 Jul 25.


Background: Small benign insulinomas are hard to localise, leading to difficulties in planning of surgical interventions. We aimed to prospectively assess the insulinoma detection rate of single-photon emission CT in combination with CT (SPECT/CT) with a glucagon-like peptide-1 receptor avid radiotracer, and compare detection rates with conventional CT/MRI techniques.

Methods: In our prospective imaging study, we enrolled adults aged 25-81 years at centres in Germany, Switzerland, and the UK. Eligible patients had proven clinical and biochemical endogenous hyperinsulinaemic hypoglycaemia and no evidence for metastatic disease on conventional imaging. CT/MRI imaging was done at referring centres according to standard protocols. At three tertiary nuclear medicine centres, we used whole body planar images and SPECT/CT of the abdomen up to 168 h after injection of (111)In-[Lys40(Ahx-DTPA-(111)In)NH2]-exendin-4 ((111)In-DTPA-exendin-4) to identify insulinomas. Consenting patients underwent surgery and imaging findings were confirmed histologically.

Findings: Between Oct 1, 2008, and Dec 31, 2011, we recruited 30 patients. All patients underwent (111)In-DTPA-exendin-4 imaging, 25 patients underwent surgery (with histological analysis), and 27 patients were assessed with CT/MRI. (111)In-DTPA-exendin-4 SPECT/CT correctly detected 19 insulinomas and four additional positive lesions (two islet-cell hyperplasia and two uncharacterised lesions) resulting in a positive predictive value of 83% (95% CI 62-94). One true negative (islet-cell hyperplasia) and one false negative (malignant insulinoma) result was identified in separate patients by (111)In-DTPA-exendin-4 SPECT/CT. Seven patients (23%) were referred to surgery on the basis of (111)In-DTPA-exendin-4 imaging alone. For 23 assessable patients, (111)In-DTPA-exendin-4 SPECT/CT had a higher sensitivity (95% [95% CI 74-100]) than did CT/MRI (47% [27-68]; p=0.011).

Interpretation: (111)In-DTPA-exendin-4 SPECT/CT could provide a good second-line imaging strategy for patients with negative results on initial imaging with CT/MRI.

Funding: Oncosuisse, the Swiss National Science Foundation, and UK Department of Health.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Exenatide
  • Female
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Indium Radioisotopes* / metabolism
  • Insulinoma / diagnostic imaging*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pentetic Acid*
  • Peptides* / metabolism
  • Receptors, Glucagon / metabolism
  • Tomography, Emission-Computed / methods*
  • Tomography, Emission-Computed, Single-Photon / methods*
  • Venoms* / metabolism


  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Indium Radioisotopes
  • Peptides
  • Receptors, Glucagon
  • Venoms
  • Pentetic Acid
  • Exenatide