Increased Expression of GLP-1R in Proliferating Islets of Men1 Mice is Detectable by [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 /PET

Sci Rep. 2018 Jan 15;8(1):748. doi: 10.1038/s41598-017-18855-0.

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment. Glucagon-like peptide 1 (GLP-1) pathway is essential in islet regeneration, i.e. inhibition of β-cell apoptosis and enhancement of β-cell proliferation, yet involvement of GLP-1 in MEN1 related P-NET has not yet been demonstrated. The objective of this work was to investigate if normal sized islets of Men1 heterozygous mice have increased Glucagon-like peptide-1 receptor (GLP-1R) expression compared to wild type islets, and if this increase is detectable in vivo with positron emission tomography (PET) using [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 (68Ga-Exendin-4). 68Ga-Exendin-4 showed potential for early lesion detection in MEN1 pancreas due to increased GLP1R expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Neuroendocrine / diagnostic imaging*
  • Carcinoma, Neuroendocrine / pathology
  • Glucagon-Like Peptide-1 Receptor / analysis*
  • Heterozygote*
  • Mice
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / pathology
  • Positron-Emission Tomography / methods*
  • Proto-Oncogene Proteins / genetics*

Substances

  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Men1 protein, mouse
  • Proto-Oncogene Proteins