Discovering new inhibitors of pancreatic NET glucose consumption

Peter M. Clark, PhD

Year: 2020
Institution: Los Angeles, The Regents of the University of California
Country: United States
State: CA
Award Type: Pilot
NET Type: Pancreas
Science Type: Basic

General Description

Well-differentiated neuroendocrine tumors (NETs) express high levels of the transmembrane somatostatin receptor subtype 2 (sstr2). Diagnostic and therapeutic radionuclides targeting this receptor have been successful in the clinic, resulting in the FDA-approval of 68Ga-DOTA-TATE for NET imaging and the pending application of peptide receptor radiotherapy (PRRT) 177Lu-DOTA-TATE for treatment of advanced disease. We have utilized a pre-clinical murine model of well-differentiated pancreatic neuroendocrine tumor (PanNET) to study SSTR2-based radionuclide imaging and therapy. The Pdx1-Cre, Men1f/f mouse model was previously characterized and produces a spectrum of islet cell phenotypes from hyperplasia to neoplasia. Using this model, we documented SSTR2 membrane expression in neoplastic islets that can be detected by SSTR2-based in-vivo imaging, and have successfully treated tumor-bearing mice with PRRT. In addition, a recently developed xenograft model of PanNET has been established that can be detected with 68Ga-DOTA-TATE and harbors an MEN1 mutation.