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

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Title: Electron Paramagnetic Resonance Implemented with Multiple Harmonic Detections Successfully Maps Extracellular pH In Vivo
Authors: Nakaoka, Ririko Browse this author
Kato, Kazuhiro Browse this author
Yamamoto, Kumiko Browse this author
Yasui, Hironobu Browse this author →KAKEN DB
Matsumoto, Shingo Browse this author →KAKEN DB
Kirilyuk, Igor A. Browse this author
Khramtsov, Valery V. Browse this author
Inanami, Osamu Browse this author →KAKEN DB
Hirata, Hiroshi Browse this author →KAKEN DB
Issue Date: 28-Feb-2023
Publisher: American Chemical Society
Journal Title: Analytical chemistry
Volume: 95
Issue: 8
Start Page: 3940
End Page: 3950
Publisher 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.
Type: article
URI: http://hdl.handle.net/2115/88566
Appears in Collections:情報科学院・情報科学研究院 (Graduate School of Information Science and Technology / Faculty of Information Science and Technology) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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