Real‐Time Metabolic Magnetic Resonance Spectroscopy of Pancreatic and Colon Cancer Tumor‐Xenografts with Parahydrogen Hyperpolarized 1‐13C Pyruvate‐d3

Abstract

AbstractParahydrogen‐induced polarization (PHIP) is an emerging technique to enhance the signal of stable isotope metabolic contrast agents for Magnetic Resonance (MR). The objective of this study is to continue establishing 1‐13C‐pyruvate‐d3, signal‐enhanced via PHIP, as a hyperpolarized contrast agent, obtained in seconds, to monitor metabolism in human cancer. Our focus was on human pancreatic and colon tumor xenografts. 1‐13C‐vinylpyruvate‐d6 was hydrogenated using parahydrogen. Thereafter, the polarization of the protons was transferred to 13C. Following a workup procedure, the free hyperpolarized 1‐13C‐pyruvate‐d3 was obtained in clean aqueous solution. After injection into animals bearing either pancreatic or colon cancer xenografts, slice‐selective MR spectra were acquired and analyzed to determine rate constants of metabolic conversion into lactate and alanine. 1‐13C‐pyruvate‐d3 proved to follow the increased metabolic rate to lactate and alanine in the tumor xenografts.