title: Positron emission tomography imaging of the glucagon-like peptide-1 receptor in healthy and streptozotocin-induced diabetic pigs.
abstract: OBJECTIVE
  The glucagon-like peptide-1 receptor (GLP-1R) has been proposed as a target for molecular imaging of beta cells. The feasibility of non-invasive imaging and quantification of GLP-1R in pancreas using the positron emission tomography (PET) tracer [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 in non-diabetic and streptozotocin (STZ)-induced diabetic pigs treated with insulin was investigated.
  
  
  METHODS
  Non-diabetic (n = 4) and STZ-induced diabetic pigs (n = 3) from the same litter were examined. Development of diabetes was confirmed by blood glucose values, clinical examinations and insulin staining of pancreatic sections post mortem. Tissue perfusion in the pancreas and kidneys was evaluated by [(15)O]water PET/computed tomography (CT) scans. The in vivo receptor specificity of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 was assessed by administration of either tracer alone or by competition with 3-6.5 μg/kg of Exendin-4. Volume of distribution and occupancy in the pancreas were quantified with a single tissue compartment model.
  
  
  RESULTS
  [(15)O]water PET/CT examinations showed reduced perfusion in the pancreas and kidneys in diabetic pigs. [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 uptake in the pancreas of both non-diabetic and diabetic pigs was almost completely abolished by co-injection of unlabeled Exendin-4 peptide. [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 uptake did not differ between non-diabetic and diabetic pigs. In all animals, administration of the tracer resulted in an immediate increase in the heart rate (HR).
  
  
  CONCLUSIONS
  Pancreatic uptake of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 was not reduced by destruction of beta cells in STZ-induced diabetic pigs.
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Lovisa
authors.initials: L
authors.lastname: Nalin
authors.forename: Ram K
authors.initials: RK
authors.lastname: Selvaraju
authors.forename: Irina
authors.initials: I
authors.lastname: Velikyan
authors.forename: Marie
authors.initials: M
authors.lastname: Berglund
authors.forename: Susanne
authors.initials: S
authors.lastname: Andréasson
authors.forename: Anna
authors.initials: A
authors.lastname: Wikstrand
authors.forename: Anneli
authors.initials: A
authors.lastname: Rydén
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Fouad
authors.initials: F
authors.lastname: Kandeel
authors.forename: Görel
authors.initials: G
authors.lastname: Nyman
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.forename: Olof
authors.initials: O
authors.lastname: Eriksson
authors.forename: Marianne
authors.initials: M
authors.lastname: Jensen-Waern
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006262:Health; D006339:Heart Rate / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D008297:Male; D049268:Positron-Emission Tomography / Q000009:adverse effects / Q000379:methods*; D011849:Radioactive Tracers; D018027:Receptors, Glucagon / Q000378:metabolism*; D013552:Swine; D014867:Water / Q000378:metabolism
chemical_list: D015415:Biomarkers; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D011849:Radioactive Tracers; D018027:Receptors, Glucagon; D014867:Water