Fecher, D.D.FecherSchwarz, T.T.SchwarzNietzer, S.S.NietzerWalles, HeikeHeikeWallesDandekar, G.G.DandekarLückerath, K.K.LückerathSteinke, M.M.Steinke2022-03-052022-03-052016https://publica.fraunhofer.de/handle/publica/244523Tumor models in 2D cell culture neglect several aspects concerning the microenvironment, which might influence tumor-biology and alter drug response. We therefore aimed to build a tumor model based on acellular rat lung scaffolds which can be combined with a bioreactor and monitored non-invasively by positron-emission-tomography (PET). Lung adenocarcinoma cell lines were cultured on acellular rat scaffolds for 14 days. A bioreactor was developed to induce ventilation and enable perfusion of the vascular system. Statically cultured tumor models treated with gefitinib, an EGFR-inhibitor were examined histologically and by FDG-PET-scans Tumor cells formed distinct clusters on the scaffold, exhibited up-regulation of carcinoma-associated marker and a reduced proliferation-rate, compared to 2D culture. FDG-PET allowed detecting and tracking of individual tumor lesions over time. Correlation of autoradiography with DAPI staining verified specific FDG uptake by tumor cells. Treatment with gefitinib reduced FDG uptake in EGFR-mutated but not in -wildtype tumor cells. Interestingly, EGFR-mutant tumor clusters varied in their response to gefitinib. This organotypic tumor model provides tumor nodules with a tumor relevant gene expression and proliferation rate. This reflects the in vivo situation better, compared to 2D culture models. Assessment of single tumor lesions and their response to treatment is possible using mPET imaging. The different responses of distinct tumor nodules indicate heterogeneity in our models. This might allow longitudinal studies regarding tumor growth and metabolism as well as preclinical testing and development of strategies against resistant sub-clones.enjournal article