title: Human Organotypic Lung Tumor Models: Suitable For Preclinical 18F-FDG PET-Imaging.
abstract: Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and -testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.
authors: Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
authors: David
authors: D
authors: Fecher
authors: Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
authors: Elisabeth
authors: E
authors: Hofmann
authors: Department of Nuclear Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
authors: Andreas
authors: A
authors: Buck
authors: Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.
authors: Ralph
authors: R
authors: Bundschuh
authors: Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
authors: Sarah
authors: S
authors: Nietzer
authors: Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.|Translational Center ´Regenerative Therapies for Oncology and Musculoskeletal Diseases`Wuerzburg, branch of the Fraunhofer Institute Interfacial Engineering and Biotechnology (IGB), Wuerzburg, Germany.
authors: Gudrun
authors: G
authors: Dandekar
authors: Department of Cardiothoracic Surgery, University Hospital Wuerzburg, Wuerzburg, Germany.
authors: Thorsten
authors: T
authors: Walles
authors: Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.|Translational Center ´Regenerative Therapies for Oncology and Musculoskeletal Diseases`Wuerzburg, branch of the Fraunhofer Institute Interfacial Engineering and Biotechnology (IGB), Wuerzburg, Germany.
authors: Heike
authors: H
authors: Walles
authors: Department of Nuclear Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
authors: Katharina
authors: K
authors: Lückerath
authors: Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.|Translational Center ´Regenerative Therapies for Oncology and Musculoskeletal Diseases`Wuerzburg, branch of the Fraunhofer Institute Interfacial Engineering and Biotechnology (IGB), Wuerzburg, Germany.
authors: Maria
authors: M
authors: Steinke
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D000077156:Gefitinib; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional / Q000379:methods; D008168:Lung / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D049268:Positron-Emission Tomography / Q000379:methods*; D011799:Quinazolines / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000077156:Gefitinib