Abstract A46: A novel patient-derived approach for preclinical evaluation of predictive imaging biomarkers in early lung cancer

Abstract Background: Lung cancer is the number one cause of cancer-related death, and lung adenocarcinoma (LUAD) is the most frequent type. Lung screening with computed tomography has allowed detection of early nodules that need diagnostic definition. We have identified the sodium-dependent glucose transporter 2 (SGLT2) as a novel diagnostic and therapeutic target that may aid the identification and the treatment of early LUAD. However, a limitation of these studies is the lack of experimental models of early cancer. Patient-derived xenografts (PDXs) are a reliable tool of translational oncology. However, the establishment of PDXs from early-stage, low-grade LUAD is characterized by low efficiency and extremely long experimental times. To study the predictive value of SGLT2 activity in early LUAD, we have established an alternative model based on a double culture system: 1) implantation of tumor tissue on the chorioallantoic membrane (CAM) of the chicken egg (in ovo system), which can be imaged only 1 week after the patient surgery; 2) growth of tumor spheroids in 3D in vitro culture, to test response to treatments. Methods: Each PDX of LUAD is divided in two specimens: one for in ovo growth in the CAM assay and one for the 3D culture as tumor spheroids. The CAM xenografts are imaged with two different tracers to characterize glucose uptake: [18F] fluorodeoxyglucose (FDG), to measure GLUT activity, and 4-[18F] fluorodeoxyglucose (Me4FDG), to assess sodium-dependent glucose transport (SGLT). The PD-tumor spheroids are cultured in 96-well plates and used for treatment with SGLT2 inhibitors as well as other drugs. Results: PET imaging of LUADs with FDG and Me4FDG revealed the presence of both glucose transporters, GLUT1 and SGLT2. Treatment of the tumor spheroids with SGLT2 inhibitors reduced cell viability and caused integrity loss in a dose-dependent manner. Conclusion: The CAM xenograft model is a useful model for implanting PD tumor fragments and studying glucose metabolism in ovo by PET imaging with very short experimental times. Tumor fragments connect to the chicken embryo vasculature within 3-5 days, so that PD material can be analyzed soon after surgery. The Me4FDG uptake in the CAM system predicts the treatment response of tumor spheroids cultured in vitro from the same PD samples. Citation Format: Eva J. Koziolek, Desiree Martin, Jie Liu, Jorge R. Barrio, W. Dean Wallace, David B. Shackelford, Jane Yanagawa, Steven Dubinett, Claudio Scafoglio. A novel patient-derived approach for preclinical evaluation of predictive imaging biomarkers in early lung cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A46.