¹⁸F-Labelled exendin to image GLP-1 receptor-expressing tissues: from niche to blockbuster?

Excerpt

Since the discovery of radiolabelled octreotide and the successful introduction into clinical practice of Octreoscan®, it has been expected that radiolabelled peptides would become a new class of radiopharmaceuticals for cancer imaging. Indeed, a series of receptor binding peptide analogues, such as cholecystokinin (CCK)/gastrin, bombesin, vasoactive intestinal protein, neurotensin and others, has been tested for imaging receptor-expressing tumours in animal models. However, clearly their introduction into clinical practice is still awaited. In this issue of the European Journal of Nuclear Medicine and Molecular Imaging, Kiesewetter et al. describe the feasibility of imaging insulinoma with ¹⁸F-labelled exendin [5], which could be considered as a major step forward in the development of another peptide-based tracer for tumour imaging. Exendin was tested more than a decade ago for the first time to image tumours expressing the glucagon-like peptide (GLP-1) receptor on their cell surface [4]. Exendin is a 39-amino acid peptide found in the saliva of the Gila monster, which binds to the incretin hormone receptor, GLP-1R. This receptor is expressed generally in low amounts in specific tissue compartments of several organs, such as pancreas, intestine, lung, kidney, breast and brain [7]. The endogenous ligands of the GLP-1R, GLP-1 and gastric inhibitory peptide are rapidly degraded by the enzyme dipeptidyl peptidase IV [8]. Therefore, the GLP-1 analogue exendin was proposed for targeting GLP-1R-expressing tumours. Among others, the GLP-1R is especially expressed in insulinomas, particularly the more common benign tumours [7]. Although insulinomas are a rare tumour type with an incidence estimated at one to four new cases per million people per year, the clinical relevance of insulinoma imaging lies in the exact preoperative localization of the tumours. This could help the surgeon in planning accurate resection, thus potentially reducing surgical complications [9]. …