Abstract 2464: In vivo imaging of ovarian and non-small cell lung cancer models hosted in the Sprague-Dawley Rag2 -/-Il2rg -/- SRG rat

Abstract

Abstract Human cancer xenografts are a vital tool for understanding tumor biology, growth kinetics, and therapeutic efficacy using animal models. While in vivo studies are traditionally done in immunocompromised mice, we have created a Sprague Dawley Rag2 -/-, Il2rg -/- rat (SRG࣪ OncoRat®) that is an excellent host for human xenografts. Lacking B, T, and NK cells, the SRG rat readily supports the growth of multiple human cancer cell lines, including lines that do not engraft well or grow consistently in existing mouse models. In vivo luminescent imaging has routinely been used in mouse models, and is particularly useful for studying orthotopic xenografts or metastatic models. In this study, we validated the SRG rat as a model that can effectively be used for in vivo imaging of human cancers. For the current study, we assessed two tumor models. Ovarian cancer cell line OV81.2-luc is a luciferase positive cell line that was generated from ascites collection from a grade IIIC, serous ovarian carcinoma. Orthotopic tumors were established by inoculating OV81.2-luc cells intraperitoneally into female SRG rats and female NSG mice, which were treated with either vehicle or cisplatin chemotherapy for 28 days. Human non-small cell lung cancer line H358-luc is a luciferase positive cell line that, when injected subcutaneously into the hind flank of SRG rats, metastasizes to the lungs. Tumors were established by inoculating H358-luc cells subcutaneously into male SRG rats, and measured thrice weekly with calipers. For both studies, tumorgenicity was measured via weekly in vivo luciferase imaging using Spectral Instruments AMI HT system. Tumors established rapidly for both OV81.2-luc and H358-luc in both SRG rats and NSG mice, with visible luciferin positive signal starting one week post cell inoculation. In OV81.2-luc hosting animals, upon necropsy, tumors were found on multiple abdominal organs including the peritoneum, ovary, mesentery, intestines, kidneys, liver, and body cavity wall. Metastatic events outside the abdominal cavity were not evident in OV81.2-luc hosting animals. In H358-luc tumor bearing rats, a high metastatic tumor burden was found in the lungs. These data confirm that the SRG rat is an excellent host for studying human cancer when compared to commonly used immunodeficient mouse models. Data demonstrate that the SRG rat has a high utility for studies using both in vivo imaging, such as orthotopic tumor implantation, and studies on metastasis. As the most immunodeficient rat commercially available, the SRG rat retains the ability to establish human tumors while possessing size, physiology, and metabolism-based advantages when compared to mice. Citation Format: Diane Begemann, Fallon Noto. In vivo imaging of ovarian and non-small cell lung cancer models hosted in the Sprague-Dawley Rag2 -/-Il2rg -/- SRG rat [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2464.