2. Academic Validation
  3. Electron Paramagnetic Resonance Implemented with Multiple Harmonic Detections Successfully Maps Extracellular pH In Vivo

Electron Paramagnetic Resonance Implemented with Multiple Harmonic Detections Successfully Maps Extracellular pH In Vivo

  • Anal Chem. 2023 Feb 1. doi: 10.1021/acs.analchem.2c03194.
Ririko Nakaoka 1,  Kazuhiro Kato 2,  Kumiko Yamamoto 2,  Hironobu Yasui 3,  Shingo Matsumoto 4,  Igor A Kirilyuk 5,  Valery V Khramtsov 6,  Osamu Inanami 3,  Hiroshi Hirata 4
Affiliations

Affiliations

  • 1 Division of Bioengineering and Bioinformatics, Graduate School of Information Science and Technology, Hokkaido University, North 14, West 9, Kita-ku, Sapporo060-0814, Japan.
  • 2 Laboratory of Radiation Biology, Graduate School of Veterinary Medicine, Hokkaido University, North 18, West 9, Kita-ku, Sapporo060-0818, Japan.
  • 3 Laboratory of Radiation Biology, Faculty of Veterinary Medicine, Hokkaido University, North 18, West 9, Kita-ku, Sapporo060-0818, Japan.
  • 4 Division of Bioengineering and Bioinformatics, Faculty of Information Science and Technology, Hokkaido University, North 14, West 9, Kita-ku, Sapporo060-0814, Japan.
  • 5 N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, 9, Ac. Lavrentieva Ave., Novosibirsk630090, Russia.
  • 6 Department of Biochemistry and Molecular Medicine, and In Vivo Multifunctional Magnetic Resonance Center, West Virginia University Robert C. Byrd Health Sciences Center, 1 Medical Center Drive, Morgantown, West Virginia26506, United States.
PMID: 36725678 DOI: 10.1021/acs.analchem.2c03194
Abstract

Extracellular acidification indicates a metabolic shift in Cancer cells and is, along with tissue hypoxia, a hallmark of tumor malignancy. Thus, non-invasive mapping of extracellular pH (pHe) is essential for researchers to understand the tumor microenvironment and to monitor tumor response to metabolism-targeting drugs. While electron paramagnetic resonance (EPR) has been successfully used to map pHe in mouse xenograft models, this method is not sensitive enough to map pHe with a moderate amount of exogenous pH-sensitive probes. Here, we show that a modified EPR system achieves twofold higher sensitivity by using the multiple harmonic detection (MHD) method and improves the robustness of pHe mapping in mouse xenograft models. Our results demonstrate that treatment of a mouse xenograft model of human-derived pancreatic ductal adenocarcinoma cells with the Carbonic Anhydrase IX (CAIX) inhibitor U-104 delays tumor growth with a concurrent tendency toward further extracellular acidification. We anticipate that EPR-based pHe mapping can be expanded to monitor the response of other metabolism-targeting drugs. Furthermore, pHe monitoring can also be used for the development of improved metabolism-targeting Cancer treatments.

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