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Abstract #0019

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

Friederike Hesse1,2, Flaviu Bulat1,3, Felix Kreis1, and Kevin M. Brindle1,4
1CRUK CI, University of Cambridge, Cambridge, United Kingdom, 2Department of Radiology, University of Cambridge, Cambridge, United Kingdom, 3Department of Chemistry, University of Cambridge, Cambridge, United Kingdom, 4Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom

Synopsis

Keywords: Deuterium, Molecular Imaging

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.

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Keywords