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Determining the minimum injected [2,3-2H2]fumarate concentration required for deuterium metabolic imaging of tumor cell death post-treatment

Abstract:
2H MRI measurements of labeled malate production following intravenous injection of 2H-labeled fumarate (1 g/kg) have been used to detect tumor cell death post-treatment in pre-clinical tumor models. We show here that much lower concentrations of 2H-labeled fumarate (0.1, 0.3 and 0.5 g/kg) can still generate a significant increase in malate concentration post-treatment, which should facilitate clinical translation. Mice were implanted subcutaneously with a triple-negative breast cancer model (MDA-MB-231) and treated with three different concentrations of a TRAIL-R2 agonist (MEDI3039). The different degrees of cell death obtained were linearly correlated with the malate/fumarate signal ratio and the absolute malate concentration.
Authors:
F Hesse, F Bulat, F Kreis, K Brindle
Journal:
Proceedings of the International Society for Magnetic Resonance in Medicine ... Scientific Meeting and Exhibition.
Publication date:
19th May 2023
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