Hyperpolarized [1-13C]pyruvate and [1,4-13C]fumarate Magnetic Resonance Spectroscopy Can Detect Response to the Vascular Disrupting Agent, Combretastatin-A4-Phosphate

Sarah E. Bohndiek^1,2, Mikko I. Kettunen^1,2, De-en Hu^1,2, Timothy H. Witney^1,2, Ferdia A. Gallagher^1,2, Kevin M. Brindle^1,2

Hyperpolarization dramatically increases the sensitivity of the 13C magnetic resonance experiment, allowing the uptake and metabolism of hyperpolarized substrates to be followed in vivo. Vascular disrupting agents target the proliferating endothelial cells in tumour vasculature, so rarely cause tumour shrinkage. Our aim was to assess whether hyperpolarized [1-13C]pyruvate and [1,4-13C]fumarate magnetic resonance spectroscopy could detect response to treatment with Combretastatin-A4-Phosphate within 24 hours of treatment and to compare these methods with data obtained by Dynamic Contrast Enhanced MRI (using Gd-DTPA) and Diffusion Weighted Imaging.