Ga-Labeled NODAGA-conjugated ghrelin receptor agonists and inverse agonists

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).