107. Assessment of 213Bi-anti-EGFR MAb treatment efficacy in malignant cancer cells with [1-13C]pyruvate and [18F]FDG

Benedikt Feuerecker, Michael Michalik, Christian Hundshammer, Markus Schwaiger, Frank Bruchertseifer, Alfred Morgenstern and Christof Seidl, Scientific Reports, (2019) DOI: 10.1038/s41598-019-44484-w

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. 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.