Timothy H. Witney1,2, Mikko I. Kettunen1,2,
De-en Hu1,2, Ferdia A. Gallagher1,2, Kevin M. Brindle1,2
1Department of Biochemistry, University
of Cambridge, Cambridge, Cambridgeshire, United Kingdom; 2Cancer
Research UK Cambridge Research Institute, Cambridge, Cambridgeshire, United
Kingdom
In
the current study, we used a co-administration of hyperpolarized [1-13C]pyruvate
and [1,4-13C2]fumarate as a sensitive marker of cell
death in a model of human breast adenocarcinoma following treatment with a
DNA damaging agent. The results show that a decrease in pyruvate - lactate
exchange coincides with the induction of cell death in breast cancer cells
both in vitro and in vivo, with an increase in fumarate
- malate exchange shown to correlate to the onset of necrosis.