Synthesis and evaluation of (S)-2-(2-[18F]fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbamoyl]-methyl)-benzoic acid ([18F]repaglinide): a promising radioligand for quantification of pancreatic beta-cell mass with positron emission tomography (PET)

Nucl Med Biol. 2004 Jul;31(5):639-47. doi: 10.1016/j.nucmedbio.2004.01.007.


18F-labeled non-sulfonylurea hypoglycemic agent (S)-2-(2-[(18)F]fluoroethoxy)-4-((3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl)-methyl)-benzoic acid ([(18)F]repaglinide), a derivative of the sulfonylurea-receptor (SUR) ligand repaglinide, was synthesized as a potential tracer for the non-invasive investigation of the sulfonylurea 1 receptor status of pancreatic beta-cells by positron emission tomography (PET) in the context of type 1 and type 2 diabetes. [(18)F]Repaglinide could be obtained in an overall radiochemical yield (RCY) of 20% after 135 min with a radiochemical purity higher than 98% applying the secondary labeling precursor 2-[(18)F]fluoroethyltosylate. Specific activity was in the range of 50-60 GBq/micromol. Labeling was conducted by exchanging the ethoxy-moiety into a 2-[(18)F]fluoroethoxy group. To characterize the properties of fluorinated repaglinide, the affinity of the analogous non-radioactive (19)F-compound for binding to the human SUR1 isoform was assessed. [(19)F]Repaglinide induced a complete monophasic inhibition curve with a Hill coefficient close to 1 (1.03) yielding a dissociation constant (K(D)) of 134 nM. Biological activity was proven via insulin secretion experiments on isolated rat islets and was comparable to that of repaglinide. Finally, biodistribution of [(18)F]repaglinide was investigated in rats by measuring the concentration of the compound in different organs after i.v. injection. Pancreatic tissue displayed a stable accumulation of approximately 0.12% of the injected dose from 10 min to 30 min p.i. 50% of the radioactive tracer could be displaced by additional injection of unlabeled repaglinide, indicating that [(18)F]repaglinide might be suitable for in vivo investigation with PET.

Publication types

  • Comparative Study
  • Evaluation Study
  • Validation Study

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Carbamates / chemical synthesis
  • Carbamates / pharmacokinetics*
  • Feasibility Studies
  • Fluorine Radioisotopes / chemistry
  • Fluorine Radioisotopes / pharmacokinetics
  • Islets of Langerhans / diagnostic imaging*
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Isotope Labeling / methods
  • Metabolic Clearance Rate
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Organ Specificity
  • Piperidines / chemical synthesis
  • Piperidines / pharmacokinetics*
  • Positron-Emission Tomography / methods*
  • Potassium Channels, Inwardly Rectifying
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Inbred Lew
  • Rats, Sprague-Dawley
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Tissue Distribution


  • ABCC8 protein, human
  • ATP-Binding Cassette Transporters
  • Abcc8 protein, rat
  • Carbamates
  • Fluorine Radioisotopes
  • Multidrug Resistance-Associated Proteins
  • Piperidines
  • Potassium Channels, Inwardly Rectifying
  • Radiopharmaceuticals
  • Receptors, Drug
  • Sulfonylurea Receptors
  • repaglinide