Hyperpolarized product selective saturating-excitations for determination of changes in metabolic reaction rates in real-time

Talia Harris, Sivaranjan Uppala, Naama Lev-Cohain, Yael Adler-Levy, David Shaul, Atara Nardi-Schreiber, Gal Sapir, Assad Azar, Ayelet Gamliel, Jacob Sosna, J. Moshe Gomori, Rachel Katz-Brull*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Investigation of hyperpolarized substrate metabolism has been showing utility in real-time determination of in-cell and in vivo enzymatic activities. Intracellular reaction rates may vary during the course of a measurement, even on the very short time scales of visibility on hyperpolarized MR, due to many factors such as the availability of the substrate and co-factors in the intracellular space. Despite this potential variation, the kinetic analysis of hyperpolarized signals typically assumes that the same rate constant (and in many cases, the same rate) applies throughout the course of the reaction as observed via the build-up and decay of the hyperpolarized signals. We demonstrate here an acquisition approach that can null the need for such an assumption and enable the detection of instantaneous changes in the rate of the reaction during an ex vivo hyperpolarized investigation, (i.e. in the course of the decay of one hyperpolarized substrate dose administered to a viable tissue sample ex vivo). This approach utilizes hyperpolarized product selective saturating-excitation pulses. Similar pulses have been previously utilized in vivo for spectroscopic imaging. However, we show here favorable consequences to kinetic rate determinations in the preparations used. We implement this acquisition strategy for studies on perfused tissue slices and develop a theory that explains why this particular approach enables the determination of changes in enzymatic rates that are monitored via the chemical conversions of hyperpolarized substrates. Real-time changes in intracellular reaction rates are demonstrated in perfused brain, liver, and xenograft breast cancer tissue slices and provide another potential differentiation parameter for tissue characterization.

Original languageAmerican English
Article numbere4189
JournalNMR in Biomedicine
Volume33
Issue number2
DOIs
StatePublished - 1 Feb 2020

Bibliographical note

Funding Information:
This project has received funding from the FP7 Ideas: European Research Council (ERC) under grant agreement No. 338040 and from the Horizon 2020 Framework Programme research and innovation program under grant agreement No. 667192.

Publisher Copyright:
© 2019 John Wiley & Sons, Ltd.

Keywords

  • MCF7 tumors
  • [1-C]pyruvate
  • alanine
  • bicarbonate
  • brain slices
  • hyperpolarized C-NMR
  • lactate
  • liver slices

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