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|Title:||Assessment of 213Bi-anti-EGFR MAb treatment efficacy in malignant cancer cells with [1-13C]pyruvate and [18F]FDG|
|Authors:||FEUERECKER BENEDIKT; MICHALIK MICHAEL; HUNDSHAMMER CHRISTIAN; SCHWAIGER M.; BRUCHERTSEIFER FRANK; MORGENSTERN ALFRED; SEIDL C.|
|Citation:||SCIENTIFIC REPORTS vol. 9 no. 1 p. 8294|
|Publisher:||NATURE PUBLISHING GROUP|
|Type:||Articles in periodicals and books|
|Abstract:||Evaluation of response to therapy is among the key objectives of oncology. A new method to evaluate this response includes magnetic resonance spectroscopy (MRS) with hyperpolarized 13C-labelled metabolites, which holds promise to provide new insights in terms of both therapeutic efficacy and tumor cell metabolism. Human EJ28Luc urothelial carcinoma and LN18 glioma cells were treated with lethal activity concentrations of a 213Bi-anti-EGFR immunoconjugate. Treatment efficacy was controlled via analysis of DNA double-strand breaks (immunofluorescence γH2AX staining) and clonogenic survival of cells. To investigate changes in metabolism of treated cells vs controls we analyzed conversion of hyperpolarized [1-13C]pyruvate to [1-13C]lactate via MRS as well as viability of cells, lactate formation and lactate dehydrogenase activity in the cellular supernatants and [18F]FDG uptake in treated cells vs controls, respectively. Treatment of malignant cancer cells with 213Bi-anti-EGFR-MAb induced intense DNA double-strand breaks, resulting in cell death as monitored via clonogenic survival. Moreover, treatment of EJ28Luc bladder cancer cells resulted in decreased cell viability, [18F]FDG-uptake and an increased lactate export. In both EJ28Luc and LN18 carcinoma cells treatment with 213Bi-anti-EGFR-MAb triggered a significant increase in lactate/pyruvate ratios, as measured with hyperpolarized [1-13C]pyruvate. Treatment with 213Bi-anti-EGFR-MAb resulted in an effective induction of cell death in EJ28Luc and LN18 cells. Lactate/pyruvate ratios of hyperpolarized [1-13C]pyruvate proved to detect early treatment response effects, holding promise for future clinical applications in early therapy monitoring.|
|JRC Directorate:||Nuclear Safety and Security|
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