title: Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study.
abstract: 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  (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.
  
  
  BACKGROUND
  Oncosuisse, the Swiss National Science Foundation, and UK Department of Health.
authors.affiliation: Division of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Berne, Inselspital, Berne, Switzerland.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Christ
authors.affiliation: Department of Radiology, Division of Nuclear Medicine, University of Basel Hospital, Switzerland; Department of Nuclear Medicine, University Hospital Freiburg, Germany; Institute of Nuclear Medicine, University College Hospital, London, UK. Electronic address: damian.wild@usb.ch.
authors.forename: Damian
authors.initials: D
authors.lastname: Wild
authors.affiliation: Department of Radiology, Division of Nuclear Medicine, University of Basel Hospital, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ederer
authors.affiliation: Department of Nuclear Medicine, University Hospital Freiburg, Germany; Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, Villingen, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Béhé
authors.affiliation: Department of Radiology, Division of Nuclear Medicine, University of Basel Hospital, Switzerland.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Nicolas
authors.affiliation: Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK.
authors.forename: Martyn E
authors.initials: ME
authors.lastname: Caplin
authors.affiliation: Division of Endocrinology, Diabetes and Osteology, Kantonsspital, St Gallen, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Brändle
authors.affiliation: Division of Visceral Surgery, Kantonsspital, St Gallen, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Clerici
authors.affiliation: Division of Endocrinology, Diabetes and Osteology, Kantonsspital Luzern, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fischli
authors.affiliation: Division of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Berne, Inselspital, Berne, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Stettler
authors.affiliation: Institute of Nuclear Medicine, University College Hospital, London, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ell
authors.affiliation: Division of Endocrinology and Diabetology, University Hospital Freiburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Seufert
authors.affiliation: Division of Visceral Surgery, University Hospital of Berne, Inselspital, Berne, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Gloor
authors.affiliation: Institute of Pathology, University of Berne, Berne, Switzerland.
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.affiliation: Institute of Pathology, University of Berne, Berne, Switzerland.
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Reubi
authors.affiliation: Department of Radiology, Division of Nuclear Medicine, University of Basel Hospital, Switzerland.
authors.forename: Flavio
authors.initials: F
authors.lastname: Forrer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077270:Exenatide; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007205:Indium Radioisotopes / Q000378:metabolism; D007340:Insulinoma / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging*; D004369:Pentetic Acid; D010455:Peptides / Q000378:metabolism; D018027:Receptors, Glucagon / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000379:methods*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014688:Venoms / Q000378:metabolism
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007205:Indium Radioisotopes; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D004369:Pentetic Acid; D000077270:Exenatide