title: 18F-radiolabeled GLP-1 analog exendin-4 for PET/CT imaging of insulinoma in small animals.
abstract: BACKGROUND
  Insulinoma is a neuroendocrine tumor derived from the β cells of pancreatic islets. They are usually relatively inaccessible for surgical intervention. High expression levels of glucagon-like peptide-1 (GLP-1) receptor have been detected in insulinoma.
  
  
  OBJECTIVE
  The aim of the study was to evaluate the potential of F-radiolabeled GLP-1 analog exendin-4 for the diagnosis of insulinoma using PET/computed tomography imaging.
  
  
  METHODS
  The GLP-1 receptor-specific molecular probe [F]FB-exendin-4 was prepared by the conjugation of exendin-4 and N-succinimidyl-4-[F] fluorobenzoate ([F]SFB). High expression of GLP-1 by the RIN-m5f insulinoma line and GLP-1 receptor specificity were evaluated by determining the saturation curve for in-vitro binding of I-radiolabeled exendin-4 and by investigation of the competitive binding between I-radiolabeled and unlabeled exendin-4. Further, the in-vivo biodistribution and micro-PET/computed tomography images of insulinoma-bearing mice were studied.
  
  
  RESULTS
  An overall radiochemical yield of 35.6±2.3% (decay corrected, n=5) and specific radioactivity of around 30 GBq/µmol were achieved for [F]FB-exendin-4, and the radiochemical purity was over 98%. Both in-vitro and in-vivo studies confirmed the specificity of [F]FB-exendin-4 to insulinoma cells.
  
  
  CONCLUSIONS
  [F]FB-exendin-4 has been found to be an effective molecular imaging probe for detecting insulinomas.
authors: Department of Nuclear Medicine, School of Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Haifei
authors: H
authors: Wu
authors: Sheng
authors: S
authors: Liang
authors: Shuai
authors: S
authors: Liu
authors: Yu
authors: Y
authors: Pan
authors: Dengfeng
authors: D
authors: Cheng
authors: Yifan
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D001565:Benzoates / Q000378:metabolism / Q000493:pharmacokinetics; D001667:Binding, Competitive; D000077270:Exenatide; D005260:Female; D005462:Fluorine Radioisotopes; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry*; D000067757:Glucagon-Like Peptide-1 Receptor; D007340:Insulinoma / Q000175:diagnosis* / Q000000981:diagnostic imaging; D007553:Isotope Labeling; D051379:Mice; D064847:Multimodal Imaging; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D018027:Receptors, Glucagon / Q000378:metabolism; D013388:Succinimides / Q000378:metabolism / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed / Q000379:methods*; D014688:Venoms / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D001565:Benzoates; D005462:Fluorine Radioisotopes; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D013388:Succinimides; D014688:Venoms; C075713:N-succinimidyl-4-fluorobenzoate; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide