PURPOSE: The purpose of this study was to evaluate the binding specificity of the radiolabeled glucagon-like peptide 1 receptor (GLP-1R) agonist (Lys⁴⁰(DOTA)NH₂)Exendin-4 in the pancreas using a combination of ex vivo autoradiography and immunohistochemistry. PROCEDURES: Sprague-Dawley rats were administered [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 i.v. with or without unlabeled Exendin (9-39) to determine binding specificity. Similar experiments were performed using Zucker diabetic fatty (ZDF) and Zucker lean (ZLC) rats. Animals were euthanized and the pancreas was extracted, immediately frozen, and sectioned. The sections were apposed to phosphor imaging plates, scanned, and immunostained for insulin. RESULTS: Co-registration of the autoradiographic and immunohistochemical images revealed that [⁶⁴Cu] (Lys⁴⁰(DOTA)NH₂)Exendin-4 specific binding was restricted to islet cells. This binding was blocked by the co-administration of Exendin(9-39) indicating that the radiotracer uptake is mediated by GLP-1R. Uptake of [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 was greatly decreased in the pancreas of ZDF rats. CONCLUSIONS: Ex vivo autoradiography results using [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 suggest that GLP-1R agonists based on Exendin-4 are attractive PET ligands for the in vivo determination of β-cell mass.
PURPOSE: The purpose of this study was to evaluate the binding specificity of the radiolabeled glucagon-like peptide 1 receptor (GLP-1R) agonist (Lys⁴⁰(DOTA)NH₂)Exendin-4 in the pancreas using a combination of ex vivo autoradiography and immunohistochemistry. PROCEDURES: Sprague-Dawley rats were administered [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 i.v. with or without unlabeled Exendin (9-39) to determine binding specificity. Similar experiments were performed using Zucker diabetic fatty (ZDF) and Zucker lean (ZLC) rats. Animals were euthanized and the pancreas was extracted, immediately frozen, and sectioned. The sections were apposed to phosphor imaging plates, scanned, and immunostained for insulin. RESULTS: Co-registration of the autoradiographic and immunohistochemical images revealed that [⁶⁴Cu] (Lys⁴⁰(DOTA)NH₂)Exendin-4 specific binding was restricted to islet cells. This binding was blocked by the co-administration of Exendin(9-39) indicating that the radiotracer uptake is mediated by GLP-1R. Uptake of [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 was greatly decreased in the pancreas of ZDFrats. CONCLUSIONS: Ex vivo autoradiography results using [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 suggest that GLP-1R agonists based on Exendin-4 are attractive PET ligands for the in vivo determination of β-cell mass.
Authors: Martin Gotthardt; Georg Lalyko; Julliëtte van Eerd-Vismale; Boris Keil; Tino Schurrat; Michael Hower; Peter Laverman; Thomas M Behr; Otto C Boerman; Burkhard Göke; Martin Béhé Journal: Regul Pept Date: 2006-08-22
Authors: D W McCarthy; R E Shefer; R E Klinkowstein; L A Bass; W H Margeneau; C S Cutler; C J Anderson; M J Welch Journal: Nucl Med Biol Date: 1997-01 Impact factor: 2.408
Authors: Tarun Singhal; Yu-Shin Ding; David Weinzimmer; Marc D Normandin; David Labaree; Jim Ropchan; Nabeel Nabulsi; Shu-fei Lin; Marc B Skaddan; Walter C Soeller; Yiyun Huang; Richard E Carson; Judith L Treadway; Gary W Cline Journal: Mol Imaging Biol Date: 2010-09-08 Impact factor: 3.488
Authors: K Moens; H Heimberg; D Flamez; P Huypens; E Quartier; Z Ling; D Pipeleers; S Gremlich; B Thorens; F Schuit Journal: Diabetes Date: 1996-02 Impact factor: 9.461
Authors: R Mann; N Nasr; D Hadden; J Sinfield; F Abidi; S Al-Sabah; R López de Maturana; J Treece-Birch; A Willshaw; D Donnelly Journal: Biochem Soc Trans Date: 2007-08 Impact factor: 5.407
Authors: Daniel J Rubins; Xiangjun Meng; Paul McQuade; Michael Klimas; Krista Getty; Shu-An Lin; Brett M Connolly; Stacey S O'Malley; Hyking Haley; Mona Purcell; Liza Gantert; Marie Holahan; Joel Lindgren; Pär Eklund; Caroline Ekblad; Fredrik Y Frejd; Eric D Hostetler; Dinko E González Trotter; Jeffrey L Evelhoch Journal: Mol Imaging Biol Date: 2020-10-23 Impact factor: 3.488
Authors: Rajaa El Bekay; Leticia Coín-Aragüez; Diego Fernández-García; Wilfredo Oliva-Olivera; Rosa Bernal-López; Mercedes Clemente-Postigo; Javier Delgado-Lista; Alberto Diaz-Ruiz; Rocío Guzman-Ruiz; Rafael Vázquez-Martínez; Said Lhamyani; María Mar Roca-Rodríguez; Sonia Fernandez Veledo; Joan Vendrell; María M Malagón; Francisco José Tinahones Journal: Br J Pharmacol Date: 2016-04-28 Impact factor: 8.739