Department of Imaging, Merck Research Laboratories, West Point, PA 19486, USA.
Mol Imaging Biol. 2012 Feb;14(1):79-87. doi: 10.1007/s11307-011-0481-7.
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.
Sprague-Dawley rats were administered ⁶⁴CuExendin-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.
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 ⁶⁴CuExendin-4 was greatly decreased in the pancreas of ZDF rats.
Ex vivo autoradiography results using ⁶⁴CuExendin-4 suggest that GLP-1R agonists based on Exendin-4 are attractive PET ligands for the in vivo determination of β-cell mass.
本研究旨在通过结合离体放射自显影和免疫组织化学技术，评估放射性标记的胰高血糖素样肽 1 受体 (GLP-1R) 激动剂 (Lys⁴⁰(DOTA)NH₂)Exendin-4 在胰腺中的结合特异性。
Sprague-Dawley 大鼠静脉给予 ⁶⁴CuExendin-4 并同时给予或不给予未标记的 Exendin (9-39)，以确定结合特异性。使用 Zucker 糖尿病肥胖 (ZDF) 和 Zucker 瘦型 (ZLC) 大鼠进行类似的实验。动物安乐死后提取胰腺，立即冷冻并切片。将切片与磷屏贴合，扫描，并进行胰岛素免疫染色。
放射自显影和免疫组织化学图像的配准显示，⁶⁴CuExendin-4 的特异性结合仅限于胰岛细胞。这种结合被 Exendin(9-39)的共同给药所阻断，表明放射性示踪剂的摄取是由 GLP-1R 介导的。ZDF 大鼠胰腺中 ⁶⁴CuExendin-4 的摄取量大大减少。
使用 ⁶⁴CuExendin-4 的离体放射自显影结果表明，基于 Exendin-4 的 GLP-1R 激动剂是用于体内测定β细胞量的有吸引力的 PET 配体。
