title: Noninvasive Imaging of Islet Transplants with 111In-Exendin-3 SPECT/CT.
abstract: Islet transplantation is a promising treatment for type 1 diabetic patients. However, there is acute as well as chronic loss of islets after transplantation. A noninvasive imaging method that could monitor islet mass might help to improve transplantation outcomes. In this study, islets were visualized after transplantation in a rat model with a dedicated small-animal SPECT scanner by targeting the glucagonlike peptide-1 receptor (GLP-1R), specifically expressed on β-cells, with (111)In-labeled exendin-3.
  
  
  
  Targeting of (111)In-exendin-3 to GLP-1R was tested in vitro on isolated islets of WAG/Rij rats. For in vivo evaluation, 400 or 800 islets were transplanted into the calf muscle of WAG/Rij rats (6-8 wk old). Four weeks after transplantation, SPECT/CT images were acquired 1 h after injection of (111)In-labeled exendin-3. After SPECT acquisition, the muscles containing the transplant were analyzed immunohistochemically and autoradiographically.
  
  
  
  The binding assay, performed on isolated islets, showed a linear correlation between the number of islets and (111)In-exendin-3 accumulation (Pearson r = 0.98). In vivo, a 1.70 ± 0.44-fold difference in tracer uptake between 400 and 800 transplanted islets was observed. Ex vivo analysis of the islet transplant showed colocalization of tracer accumulation on autoradiography, with insulin-positive cells and GLP-1R expression on immunohistochemistry.
  
  
  
  (111)In-exendin-3 accumulates specifically in the β-cells after islet transplantation and is a promising tracer for noninvasive monitoring of the islet mass.
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands Inge.vanderKroon@radboudumc.nl.
authors.forename: Inge
authors.initials: I
authors.lastname: van der Kroon
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Karolina
authors.initials: K
authors.lastname: Andralojc
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Stefanie M A
authors.initials: SM
authors.lastname: Willekens
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Desirée
authors.initials: D
authors.lastname: Bos
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Lieke
authors.initials: L
authors.lastname: Joosten
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Brom
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Gotthardt
mesh_terms: D000818:Animals; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D007205:Indium Radioisotopes; D016381:Islets of Langerhans Transplantation; D010455:Peptides / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D007205:Indium Radioisotopes; D010455:Peptides; C066448:exendin 3
keywords: GLP-1R; SPECT; exendin-3; islet imaging; islet transplantation