The BON-SSTR2 Chicken Chorioallantoic Membrane (CAM) Model for the Analysis of Lu-17-DOTATOC Sensitizing Agents Abstract #2280

Introduction: Peptide radioreceptor therapy (PRRT) is a promising therapy option for SSTR2-positive pancreatic neuroendocrine neoplasms (NEN). However, therapeutic effects are often not satisfying concerning sensitivity to PRRT. We hypothesize that the slow proliferation of NENs provides sufficient time for the repair of beta-particle induced-DNA damage. The ubiquitin-proteasome-system is involved in DNA damage repair and affected by the proteasome inhibitor bortezomib (Velcade®). The inhibition of DNA damage repair during PRRT may be an option to improve therapy response in NEN. We have recently demonstrated the damage repair inhibitory and pro-apoptotic effect of bortezomib in NEN in vitro (Briest et al., in revision).
Aim(s): Here, we aimed to develop a useful PRRT xenograft model and present preliminary data of in vivo experiments.
Materials and methods: We established a PRRT in vivo model by inoculating SSTR2-transfected BON as tumor plaques onto the chorioallantoic membrane (CAM) of fertilized chicken eggs. We treated xenografted tumors with 20 MBq Lu-177-DOTATOC with and without bortezomib versus controls. Tumor plaques were imaged by SPECT for Lu-177-DOTATOC uptake and MRI for growth monitoring. Afterwards, plaques were explanted and analyzed by Western blot.
Conference: 15th Annual ENETS conference (2018)
Category: Basic Science - In vitro models, tumor growth, CTCs
Presenting Author: Dr. Franziska Briest

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