We are proposing to study PRRT alone and in combination with targeted therapies to identify optimal in vivo approaches for future clinical trials.
#1: Compare PRRT dosing regimens to optimize efficacy and limit toxicity using in vivo PanNET models
#2: Determine how targeted therapies affect SSTR2 expression and radionuclide imaging and treatment effectiveness in models of PanNET
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.
NET Research Foundation
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