Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate

Evaluation of treatment response is among the major challenges in modern oncology. We herein used a sequential approach to assess the metabolic responses in EJ28Luc (bladder) and LN18 (glioma) cancer cells after a targeted radionuclide-treatment followed by cultivation of the cells with 13C-labelled glucose. A monoclonal antibody targeting the EGF receptor (EGFR) was labelled with the alpha emitter 213Bi (213Bi-anti-EGFR-MAb). Both cancer cell lines, overexpressing EGFR, were incubated for 3h with the radioimmunoconjugate. To assess the responses in the core carbon metabolism upon this treatment, these cancer cell lines were subsequently cultivated 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 via glycolysis and the citrate cycle. In comparison to untreated controls, treatment of EJ28Luc cells with 213Bi-anti-EGFR-MAb resulted in a significantly decreased incorporation of [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 glioma cell line. Treatment of EJ28Luc, but not of the glioma cells with 213Bi-anti-EGFR-MAb resulted in decreased incorporation of 13C-labelled glucose into amino acids derived from glycolytic intermediates, indicative of a treatment response. These pilot experiments show that the 13C-labelling approach can be a valid tool to assess the responsivity of cancer cells upon radionuclide-treatment at high metabolic resolution.

FEUERECKER Benedikt;  BIECHL Philipp;  SEIDL C.;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  SCHWAIGER M.;  EISENREICH Wolfgang; 

2021-03-24

NATURE PUBLISHING GROUP

JRC124346

2045-2322 (online),   

https://www.nature.com/articles/s41598-021-84421-4,    https://publications.jrc.ec.europa.eu/repository/handle/JRC124346,   

10.1038/s41598-021-84421-4 (online),