Abstract 1659: Development of an orthotopic murine model of a patient-derived pancreatic adenocarcinoma to evaluate the tissue specificity of two novel fluorescent compounds

Abstract

Abstract Fluorescent dyes have been used in medical diagnostics for over 50 years. The emergence of new fluorescent imaging technology in support of surgery and the need for increased sensitivity and precision have driven the search for novel fluorescent molecules. Orthotopic patient-derived pancreatic tumor models provide a closely related human tumor within organ-specific tumor microenvironment, which was well suited to the evaluation of the tissue specificity of two novel fluorescent compounds. To this end, we have developed an orthotopic tumor model of IM-PAN-15 (PDX model developed within the IMODI consortium), a patient derived pancreatic adenocarcinoma, in mice. Tumor cells were amplified subcutaneously in SCID mice and the resulting fragments subsequently surgically implanted into the pancreas of irradiated BALB/c nude mice. Tumor development was monitored in vivo by MRI at three time points. Fluorescent compounds were injected intravenously 36 days after tumor fragment implantation, when mean tumor volumes were approximately 70 mm³. Ex-vivo fluorescent imaging showed that 2h after injection, the two novel fluorescent compounds were present in the pancreas and tumor at roughly equivalent amounts. However, 48h after injection, a clear preferential distribution for the tumor was observed, with both compounds producing an approximately four-fold higher fluorescent signal in the tumor than in the surround pancreatic tissue. This effect persisted six days after injection, although the signal decreased over time. In comparison, indocyanine green, a dye widely used in medical diagnostics, showed no specific accumulation in either the pancreas or tumor. In conclusion, we report the development of a clinically relevant, patient-derived orthotopic tumor model and demonstrate its use in the investigation of tissue specificity of two novel fluorescent compounds. Keywords: PDX, fluorescent dyes, orthotopic pancreatic model, MRI Citation Format: Olivier Duchamp, Cyril Berthet, Peggy Provent, Elodie Marie Dit Chatel, Jordan Longin, Stanislas Urbain, François Scherninski. Development of an orthotopic murine model of a patient-derived pancreatic adenocarcinoma to evaluate the tissue specificity of two novel fluorescent compounds [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1659.