Chopra Arvind
National Center for Biotechnology Information, NLM, Bethesda, MD 20894
Ghrelin is a 28-amino-acid peptide hormone that is produced and secreted mainly by the gastric mucosa and triggers the secretion of growth hormone (GH) from the pituitary by binding to the ghrelin receptor (previously known as the GH secretagogue receptor 1a or GHSR1a) (1). Although ghrelin is known to have several endocrine functions, investigators are interested in this molecule primarily because it is known to stimulate appetite, promote energy storage, and play a role in the development of obesity (1, 2). Therefore, the ghrelin/GHSR pathway is considered to be an important target for the treatment of obesity, cachexia, and anorexia (2, 3). However, ghrelin has a low stability while in circulation, and there is a lack of information regarding its behavior and biodistribution (2). In order to gain insight into the biological behavior of the ghrelin receptor, radiolabeled peptide agonists and inverse agonists (an inverse agonist binds to the same receptor as an agonist but produces an effect that is opposite to that of the agonist)) were designed and evaluated by Chollet et al. for use with positron emission tomography (PET) (2). The ghrelin agonists and inverse agonists were conjugated to 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), a bifunctional chelating agent, and labeled with Ga ([Ga]-ghrelin conjugates designated - and ). The functional behavior of the tracers was investigated and the biodistribution and imaging properties of the labeled peptides was studied in rodents (2).
胃饥饿素是一种由28个氨基酸组成的肽类激素，主要由胃黏膜产生和分泌，通过与胃饥饿素受体（以前称为生长激素促分泌素受体1a或GHSR1a）结合，触发垂体分泌生长激素（GH）(1)。尽管已知胃饥饿素具有多种内分泌功能，但研究人员对该分子主要感兴趣的原因是，已知它能刺激食欲、促进能量储存，并在肥胖症的发生发展中起作用(1, 2)。因此，胃饥饿素/GHSR途径被认为是治疗肥胖症、恶病质和厌食症的重要靶点(2, 3)。然而，胃饥饿素在循环中的稳定性较低，并且缺乏关于其行为和生物分布的信息(2)。为了深入了解胃饥饿素受体的生物学行为，Chollet等人设计并评估了放射性标记的肽激动剂和反向激动剂（反向激动剂与激动剂结合于同一受体，但产生与激动剂相反的效应），用于正电子发射断层扫描（PET）(2)。胃饥饿素激动剂和反向激动剂与双功能螯合剂1,4,7-三氮杂环壬烷-1-戊二酸-4,7-乙酸（NODAGA）偶联，并标记上镓（[Ga] -胃饥饿素偶联物，分别命名为 - 和 ）。研究了示踪剂的功能行为，并在啮齿动物中研究了标记肽的生物分布和成像特性(2)。
