P2.11-39 Multimodal Monitoring of Patient-Derived Early-Stage Lung Adenocarcinoma with the Chicken Chorioallantoic Membrane System

Abstract

Positron-emission-tomography (PET), imaging uptake of [18F] fluorodeoxyglucose (FDG), is a powerful tool for lung cancer staging, but lacks sensitivity in early lesions. We have recently discovered that early-stage lung adenocarcinoma (LUAD) depends on another system for glucose uptake, the sodium- glucose transporter 2 (SGLT2), not detected by FDG PET. The tracer methyl 4-[18F] fluorodeoxyglucose (Me4FDG) is specific for SGLTs. Because the establishment of patient-derived xenografts (PDXs) from early-stage LUAD is characterized by low efficiency and long experimental times, we have developed an alternative model to study tumor metabolism in LUAD, based on the implantation of tumor tissue on the chorioallantoic membrane (CAM) of chicken eggs (in ovo system). PDXs of LUAD were established in ovo by implanting tumor fragments or dissociated cells in matrigel onto the CAM of fertilized chicken eggs. Xenografts were grown for up to 10 days. After day 7, the eggs were imaged with FDG and Me4FDG PET to characterize glucose uptake, then rescanned with both tracers after treatment with SGLT2 inhibitor dapagliflozin to prove SGLT2 specificity of Met4FDG. Multiparametric magnetic resonance imaging (MRI) was performed to assess tumor growth, morphology (T1w, T2w, diffusion-weighted imaging) and vasculature (angiography; GadospinP). At day 10, the xenografts were harvested for histology and immunohistochemistry or reimplanted onto a new CAM for continuous passaging. FDG- and Me4FDG-PET adenocarcinomas confirmed the presence of both glucose transporters, GLUT1 and SGLT2. MRI angiography revealed that both tumor plaques and tumor fragments were connected to the embryonic vasculature. Following dapagliflozin treatment, Met4FDG uptake was successfully blocked in the PD tumor fragments. The CAM xenograft model is useful for studying the heterogeneity of glucose uptake in ovo by imaging the activity of different transporters with FDG and Me4FDG. The novel PET tracer Met4FDG allows to validate SGLT2 expression as well as its blockage by SGLT2 inhibitors gliflozins.