title: Triple-peptide receptor targeting in vitro allows detection of all tested gut and bronchial NETs.
abstract: A high proportion of gut and bronchial neuroendocrine tumors (NETs) overexpresses somatostatin receptors, especially the sst2 subtype. It has also recently been observed that incretin receptors, namely glucagonlike peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptors, can be overexpressed in gut and bronchial NETs. However, because not all tumors can express these receptors in sufficient amounts, in vivo imaging with a single radioligand may not always be successful. We therefore evaluated with in vitro methods whether a cocktail of radioligands targeting these 3 receptors would improve tumor labeling.
  
  
  METHODS
  In vitro receptor autoradiography was performed on 55 NETs, comparing in each successive section of tumor the binding with a single radioligand, either (125)I-Tyr(3)-octreotide, (125)I-GLP-1(7-36)amide, or (125)I-GIP(1-30), with the binding using a cocktail of all 3 radioligands, given concomitantly under identical experimental conditions.
  
  
  RESULTS
  Using the cocktail of radioligands, all tumors without exception showed moderate to very high binding, with a receptor density corresponding to 1,000-10,000 dpm/mg of tissue; conversely, single-ligand binding, although identifying most tumors as receptor-positive, failed to detect receptors or measured only a low density of receptors below 1,000 dpm/mg in a significant number of tumors. In addition, the cocktail of radioligands always provided a homogeneous labeling of the whole tumor, whereas single radioligands occasionally showed heterogeneous labeling.
  
  
  CONCLUSIONS
  The study suggests that the use of a cocktail of 3 radioligands binding to somatostatin receptors, GLP-1 receptors, and GIP receptors would allow detecting virtually all NETs and labeling them homogeneously in vivo, representing a significant improvement for imaging and therapy in NETs.
authors.affiliation: Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland reubi@pathology.unibe.ch.
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Reubi
authors.affiliation: Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Waser
mesh_terms: D001345:Autoradiography; D001984:Bronchial Neoplasms / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007340:Insulinoma / Q000378:metabolism; D007457:Iodine Radioisotopes; D008024:Ligands; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000737:chemistry*; D015282:Octreotide / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000378:metabolism; D011485:Protein Binding; D011964:Receptors, Gastrointestinal Hormone / Q000737:chemistry*; D018027:Receptors, Glucagon / Q000737:chemistry*; D018000:Receptors, Peptide / Q000737:chemistry*; D017481:Receptors, Somatostatin / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007457:Iodine Radioisotopes; D008024:Ligands; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; D018000:Receptors, Peptide; D017481:Receptors, Somatostatin; D014443:Tyrosine; C041086:gastric inhibitory polypeptide receptor; D015282:Octreotide
keywords: GLP-1 receptors; incretin receptors; multireceptor imaging; neuroendocrine tumors; somatostatin receptors