Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate
Abstract Evaluation of treatment response is among the major challenges in modern oncology. We herein used a monoclonal antibody targeting the EGF receptor (EGFR) labelled with the alpha emitter 213Bi (213Bi-anti-EGFR-MAb). EJ28Luc (bladder) and LN18 (glioma) cancer cells, both overexpressing EGFR,...
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2021-03-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-021-84421-4 |
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doaj-fc81492bf3d1462796b1f5eda86be0142021-03-21T12:34:25ZengNature Publishing GroupScientific Reports2045-23222021-03-0111111110.1038/s41598-021-84421-4Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugateBenedikt Feuerecker0Philipp Biechl1Christof Seidl2Frank Bruchertseifer3Alfred Morgenstern4Markus Schwaiger5Wolfgang Eisenreich6Department of Nuclear Medicine, School of Medicine, Technische Universität MünchenDepartment of Chemistry, Bavarian NMR Center-Structural Membrane Biochemistry, Technische Universität MünchenDepartment of Nuclear Medicine, School of Medicine, Technische Universität MünchenEuropean Commission, Joint Research Centre, Directorate for Nuclear Safety and SecurityEuropean Commission, Joint Research Centre, Directorate for Nuclear Safety and SecurityDepartment of Nuclear Medicine, School of Medicine, Technische Universität MünchenDepartment of Chemistry, Bavarian NMR Center-Structural Membrane Biochemistry, Technische Universität MünchenAbstract Evaluation of treatment response is among the major challenges in modern oncology. We herein used a monoclonal antibody targeting the EGF receptor (EGFR) labelled with the alpha emitter 213Bi (213Bi-anti-EGFR-MAb). EJ28Luc (bladder) and LN18 (glioma) cancer cells, both overexpressing EGFR, were incubated for 3 h with the radioimmunoconjugate. To assess the responses in the core carbon metabolism upon this treatment, these cancer cell lines were subsequently cultivated for 18 h in the presence of [U-13C6]glucose. 13C-enrichment and isotopologue profiles of key amino acids were monitored by gas chromatography–mass spectrometry (GC/MS), in order to monitor the impacts of the radionuclide-treatment upon glucose metabolism. In comparison to untreated controls, treatment of EJ28Luc cells with 213Bi-anti-EGFR-MAb resulted in a significantly decreased incorporation of 13C from [U-13C6]glucose into alanine, aspartate, glutamate, glycine, proline and serine. In sharp contrast, the same amino acids did not display less 13C-enrichments during treatment of the LN18 cells. The data indicate early treatment response of the bladder cancer cells, but not of the glioma cells though cell lines were killed following 213Bi-anti-EGFR-MAb treatment. The pilot study shows that the 13C-labelling approach is a valid tool to assess the responsiveness of cancer cells upon radionuclide-treatment in considerable metabolic detail.https://doi.org/10.1038/s41598-021-84421-4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Benedikt Feuerecker Philipp Biechl Christof Seidl Frank Bruchertseifer Alfred Morgenstern Markus Schwaiger Wolfgang Eisenreich |
spellingShingle |
Benedikt Feuerecker Philipp Biechl Christof Seidl Frank Bruchertseifer Alfred Morgenstern Markus Schwaiger Wolfgang Eisenreich Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate Scientific Reports |
author_facet |
Benedikt Feuerecker Philipp Biechl Christof Seidl Frank Bruchertseifer Alfred Morgenstern Markus Schwaiger Wolfgang Eisenreich |
author_sort |
Benedikt Feuerecker |
title |
Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate |
title_short |
Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate |
title_full |
Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate |
title_fullStr |
Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate |
title_full_unstemmed |
Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate |
title_sort |
diverse metabolic response of cancer cells treated with a 213bi-anti-egfr-immunoconjugate |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-03-01 |
description |
Abstract Evaluation of treatment response is among the major challenges in modern oncology. We herein used a monoclonal antibody targeting the EGF receptor (EGFR) labelled with the alpha emitter 213Bi (213Bi-anti-EGFR-MAb). EJ28Luc (bladder) and LN18 (glioma) cancer cells, both overexpressing EGFR, were incubated for 3 h with the radioimmunoconjugate. To assess the responses in the core carbon metabolism upon this treatment, these cancer cell lines were subsequently cultivated for 18 h in the presence of [U-13C6]glucose. 13C-enrichment and isotopologue profiles of key amino acids were monitored by gas chromatography–mass spectrometry (GC/MS), in order to monitor the impacts of the radionuclide-treatment upon glucose metabolism. In comparison to untreated controls, treatment of EJ28Luc cells with 213Bi-anti-EGFR-MAb resulted in a significantly decreased incorporation of 13C from [U-13C6]glucose into alanine, aspartate, glutamate, glycine, proline and serine. In sharp contrast, the same amino acids did not display less 13C-enrichments during treatment of the LN18 cells. The data indicate early treatment response of the bladder cancer cells, but not of the glioma cells though cell lines were killed following 213Bi-anti-EGFR-MAb treatment. The pilot study shows that the 13C-labelling approach is a valid tool to assess the responsiveness of cancer cells upon radionuclide-treatment in considerable metabolic detail. |
url |
https://doi.org/10.1038/s41598-021-84421-4 |
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