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Human Organotypic Lung Tumor Models: Suitable For Preclinical \(^{18}\)F-FDG PET-Imaging

Please always quote using this URN: urn:nbn:de:bvb:20-opus-179678
  • 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 scaffoldDevelopment 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-[\(^{18}\)F]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.show moreshow less

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Metadaten
Author: David Fecher, Elisabeth Hofmann, Andreas Buck, Ralph Bundschuh, Sarah Nietzer, Gudrun Dandekar, Thorsten Walles, Heike Walles, Katharina Lückerath, Maria Steinke
URN:urn:nbn:de:bvb:20-opus-179678
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Thorax-, Herz- u. Thorakale Gefäßchirurgie
Medizinische Fakultät / Klinik und Poliklinik für Nuklearmedizin
Medizinische Fakultät / Lehrstuhl für Tissue Engineering und Regenerative Medizin
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2016
Volume:11
Issue:8
Article Number:e0160282
Source:PLoS ONE 2016, 11(8):e0160282. DOI:10.1371/journal.pone.0160282
DOI:https://doi.org/10.1371/journal.pone.0160282
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:adenocarcinoma of the lung; cancer treatment; collagens; extracellular matrix; lung and intrathoracic tumors; pulmonary imaging; secondary lung tumors; trachea
Release Date:2021/03/24
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International