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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Autores principales:	Benedikt Feuerecker, Philipp Biechl, Christof Seidl, Frank Bruchertseifer, Alfred Morgenstern, Markus Schwaiger, Wolfgang Eisenreich
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fc81492bf3d1462796b1f5eda86be014
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spelling	oai:doaj.org-article:fc81492bf3d1462796b1f5eda86be0142021-12-02T13:18:08ZDiverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate10.1038/s41598-021-84421-42045-2322https://doaj.org/article/fc81492bf3d1462796b1f5eda86be0142021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84421-4https://doaj.org/toc/2045-2322Abstract 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.Benedikt FeuereckerPhilipp BiechlChristof SeidlFrank BruchertseiferAlfred MorgensternMarkus SchwaigerWolfgang EisenreichNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
author	Benedikt Feuerecker Philipp Biechl Christof Seidl Frank Bruchertseifer Alfred Morgenstern Markus Schwaiger Wolfgang Eisenreich
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 Portfolio
publishDate	2021
url	https://doaj.org/article/fc81492bf3d1462796b1f5eda86be014
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Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate

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