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.
Highlights
Evaluation of response to treatment of cancerous diseases is among the major challenges in modern oncology
Our aim was to use the 13C-based metabolic pathway analysis monitored by gas chromatography–mass spectrometry (GC–MS) of amino acids to comprehensively determine the impact of an alpha emitter treatment upon the core metabolic pathways in cancer cells
The activity concentration of 213Bi-anti-EGF receptor (EGFR)-MAb applied for incubation of both LN18 glioma and EJ28-luc bladder cancer cells (1.48 MBq/mL) proved to be lethal for approximately 99% of the cells
Summary
Evaluation of response to treatment of cancerous diseases is among the major challenges in modern oncology. Pyruvate carboxylation was higher at the site of lung metastases compared to the primary tumor site in breast cancer c ells[8] These examples underline the interplay between different metabolic pathways and metastatic/oncological behavior. The approach using 13C-labeled glucose is a promising concept for the evaluation of targeted therapy, because early treatment responses following incubation of cancer cells with alpha-emitter immunoconjugates still need to be clarified. We used an antibody targeting the epidermal growth factor receptor (EGRF) labelled with the alpha emitter 213Bi (213Bi-anti-EGFR-MAb), to explore treatment associated responses in two different cancer cell lines expressing EGRF. As alpha emitters have only a short range in tissue, it is necessary to warrant a close delivery of the alpha emitter to the target cells In our study, this is realized using an anti-EGFR-antibody. Potential further complications of this approach arise due to unpredictable kinetic rates of metabolic enzymes in the complex environment of human cells and the relatively short half-life of hyperpolarized substrates
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
