Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repaglinide): a potential beta-cell imaging agent

Bioorganic & Medicinal Chemistry Letters
B WänglerR Schirrmacher

Abstract

The 11C-labeled sulfonylurea receptor 1 (SUR1) ligand (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repaglinide) was synthesized in an overall radiochemical yield of 35% after 55 min with a radiochemical purity higher than 99%. This compound is considered for the noninvasive investigation of the SUR1 receptor status of pancreatic beta-cells by positron emission tomography (PET) in the context of type 1 and type 2 diabetes. The specific activity was 40-70 GBq/micromol. In vitro testing of the nonradioactive methoxy-repaglinide was performed to characterize the affinity for binding to the human SUR1 isoform. Methoxy-repaglinide induced a complete monophasic inhibition curve with a Hill coefficient close to 1 (1.03) yielding a dissociation constant (KD) of 83 nM and an IC50 of 163 nM. Insulin secretion experiments on isolated rat islets were performed to prove biological activity, which was determined to be in the same range as that of original repaglinide.

Citations

Sep 9, 2010·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Tarun SinghalGary W Cline
Feb 16, 2013·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Björn A BlombergAbass Alavi
Oct 18, 2008·Diabetes, Obesity & Metabolism·S Schneider
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Mai LinXiankai Sun
May 11, 2012·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Marc D NormandinGary W Cline
Mar 6, 2009·European Journal of Radiology·Anna Moore
Oct 19, 2004·Radiologic Clinics of North America·Chyng-Yann Shiue, Michael J Welch
Oct 19, 2006·Nuclear Medicine and Biology·Norman Ray SimpsonPaul Emerson Harris
Aug 15, 2012·Endocrine Reviews·Valentina Di GialleonardoAlberto Signore
Jun 17, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Mei-Ping KungHank F Kung
Sep 22, 2010·Advanced Drug Delivery Reviews·Zhanhong Wu, Fouad Kandeel

❮ Previous
Next ❯

Related Concepts

Related Feeds