In-cell determination of lactate dehydrogenase activity in a luminal breast cancer model – ex vivo investigation of excised xenograft tumor slices using dDNP hyperpolarized [1-13C]pyruvate

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

[1-13C]pyruvate, the most widely used compound in dissolution-dynamic nuclear polarization (dDNP) magnetic resonance (MR), enables the visualization of lactate dehydrogenase (LDH) activity. This activity had been demonstrated in a wide variety of cancer models, ranging from cultured cells, to xenograft models, to human tumors in situ. Here we quantified the LDH activity in precision cut tumor slices (PCTS) of breast cancer xenografts. The Michigan Cancer Foundation-7 (MCF7) cell-line was chosen as a model for the luminal breast cancer type which is hormone responsive and is highly prevalent. The LDH activity, which was manifested as [1- 13C]lactate production in the tumor slices, ranged between 3.8 and 6.1 nmole/nmole adenosine triphosphate (ATP) in 1 min (average 4.6 ± 1.0) on three different experimental set-ups consisting of arrested vs. continuous perfusion and non-selective and selective RF pulsation schemes and combinations thereof. This rate was converted to an expected LDH activity in a mass ranging between 3.3 and 5.2 µmole/g in 1 min, using the ATP level of these tumors. This indicated the likely utility of this approach in clinical dDNP of the human breast and may be useful as guidance for treatment response assessment in a large number of tumor types and therapies ex vivo.

Original languageAmerican English
Article number2089
JournalSensors
Volume19
Issue number9
DOIs
StatePublished - 1 May 2019

Bibliographical note

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

Publisher Copyright:
© 2019 by the authors.

Keywords

  • Breast cancer
  • C-NMR
  • Hyperpolarization
  • LDH
  • Magnetic resonance
  • Precision-cut tissue slices

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