PARTICLE THERAPY FOR THE TREATMENT OF PANCREATIC TUMORS: IN VITRO AND IN VIVO RADIOBIOLOGICAL STUDIES

<b>Background and Aims</b>: Pancreatic ductal adenocarcinoma is an aggressive type of cancer, generally discovered at advanced stages of the disease. Conventional therapies are limited, highly toxic and depend on patient fitness. Immunotherapy is not a successful option due to tumor poor immunogenicity and abundant desmoplastic stroma. In this sense, novel treatments are needed to control the tumor while preserving the surrounding structures and organs. Boron Neutron Capture Therapy (BNCT) and Protontherapy are worth exploring, due to their selectivity and organ preserving characteristics. Our laboratory has experience in the study of BNCT in different orthotopic tumor models. The aim of this study is to establish a pancreatic orthotopic tumor model in hamsters to study the potential therapeutic effect and toxicity of particle therapy, particularly BNCT and Protontherapy.<br/><br/><b>Methods</b>: Hamster pancreatic tumor cells (HapT1) were grown and amplified in DMEM high glucose supplemented with sodium bicarbonate, 10 mg/ml gentamicin and 10 % fetal bovine serum (incubation at 37°C, 5% CO₂). A small lateral subcostal laparotomy was performed in 5 hamsters under anesthesia and analgesia. HapT1 cells in 100 ul of DMEM were injected beneath the capsule of the pancreas, particularly in the splenic lobe (T0). We evaluated tumor development after injecting 10⁶ or 5x10⁵ cells and two different time-points after injection: T14 and T30 days. Samples of tumor, pancreas, stomach, intestine and spleen were fixed in formalin and stained with haematoxylin and eosin.<br/><br/><b>Results</b>: All animals developed one tumor (400-800 mm³) in the pancreas. Tumor histological evaluation showed pseudo-duct-like structures and focal deposition of extracellular matrix proteins. No macroscopic metastases were observed. All animals recovered their weight compared to T0.<br/><br/><b>Conclusions</b>: The hamster orthotopic pancreatic tumor model was reproduced in our laboratory. qPCR studies to describe the expression of boron compound transporters, immunosupressor molecules and DNA repair machinery are underway. These results will help to choose the boron compound suitable for <i>in vitro</i> /<i> in vivo</i> irradiations. Ongoing dosimetry studies and evaluation of radioprotectors will be crucial to plan animal irradiations. BNCT results in this model will also pave the way for the use of Protontherapy in this experimental model.