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

Chemistry. 2024 Sep 11;30(51):e202400187. doi: 10.1002/chem.202400187. Epub 2024 Aug 25.

Abstract

Parahydrogen-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.

Keywords: Hyperpolarization; NMR; Parahydrogen.

MeSH terms

  • Alanine / chemistry
  • Alanine / metabolism
  • Animals
  • Carbon Isotopes* / chemistry
  • Cell Line, Tumor
  • Colonic Neoplasms* / diagnostic imaging
  • Colonic Neoplasms* / metabolism
  • Contrast Media / chemistry
  • Contrast Media / metabolism
  • Humans
  • Hydrogen / chemistry
  • Lactic Acid / chemistry
  • Lactic Acid / metabolism
  • Magnetic Resonance Spectroscopy* / methods
  • Mice
  • Pancreatic Neoplasms* / diagnostic imaging
  • Pancreatic Neoplasms* / metabolism
  • Pyruvic Acid* / chemistry
  • Pyruvic Acid* / metabolism

Substances

  • Pyruvic Acid
  • Carbon Isotopes
  • Lactic Acid
  • Contrast Media
  • Alanine
  • Hydrogen
  • Carbon-13