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 β-cell mass with positron emission tomography (PET)

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RESEARCH PRODUCT

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 β-cell mass with positron emission tomography (PET)

C. Schwanstecher Oliver Thews S. Comagic C-y. Shiue Markus Piel Peter J. Feilen B Wängler M. Schwanstecher Stephan Schneider Frank Rösch A. Alavi Ralf Schirrmacher Esther Schirrmacher S. Höhnemann

subject

Fluorine Radioisotopes Cancer Research Biodistribution Metabolic Clearance Rate Receptors Drug Context (language use)Sulfonylurea Receptors Rats Sprague-Dawley Islets of Langerhans chemistry.chemical_compound Piperidines medicine Radioligand Animals Tissue Distribution Radiology Nuclear Medicine and imaging Potassium Channels Inwardly Rectifying Benzoic acid Chemistry Biological activity Ligand (biochemistry)Repaglinide Rats Dissociation constant Biochemistry Organ Specificity Rats Inbred Lew Isotope Labeling Positron-Emission Tomography Feasibility Studies Molecular Medicine ATP-Binding Cassette Transporters Carbamates Multidrug Resistance-Associated Proteins Radiopharmaceuticals Nuclear chemistry medicine.drug

description

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.

year	journal	country	edition	language
2004-01-13	Nuclear Medicine and Biology

https://doi.org/10.1016/j.nucmedbio.2004.01.007