Non-invasive electron paramagnetic resonance imaging detects tumor redox imbalance induced by ferroptosis

Targeting ferroptosis, cell death caused by the iron-dependent accumulation of lipid peroxides, and disruption of the redox balance are promising strategies in cancer therapy owing to the physiological characteristics of cancer cells. However, the detection of ferroptosis using in vivo imaging remai...

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Main Authors: Kazuhiro Kato, Hironobu Yasui, Hideo Sato-Akaba, Miho C. Emoto, Hirotada G. Fujii, Maciej M. Kmiec, Periannan Kuppusamy, Masaki Nagane, Tadashi Yamashita, Osamu Inanami
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Redox Report
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Online Access:https://www.tandfonline.com/doi/10.1080/13510002.2025.2454887
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author Kazuhiro Kato
Hironobu Yasui
Hideo Sato-Akaba
Miho C. Emoto
Hirotada G. Fujii
Maciej M. Kmiec
Periannan Kuppusamy
Masaki Nagane
Tadashi Yamashita
Osamu Inanami
author_facet Kazuhiro Kato
Hironobu Yasui
Hideo Sato-Akaba
Miho C. Emoto
Hirotada G. Fujii
Maciej M. Kmiec
Periannan Kuppusamy
Masaki Nagane
Tadashi Yamashita
Osamu Inanami
author_sort Kazuhiro Kato
collection DOAJ
description Targeting ferroptosis, cell death caused by the iron-dependent accumulation of lipid peroxides, and disruption of the redox balance are promising strategies in cancer therapy owing to the physiological characteristics of cancer cells. However, the detection of ferroptosis using in vivo imaging remains challenging. We previously reported that redox maps showing the reduction power per unit time of implanted tumor tissues via non-invasive redox imaging using a novel, compact, and portable electron paramagnetic resonance imaging (EPRI) device could be compared with tumor tissue sections. This study aimed to apply the EPRI technique to the in vivo detection of ferroptosis. Notably, redox maps reflecting changes in the redox status of tumors induced by the ferroptosis-inducing agent imidazole ketone erastin (IKE) were compared with the immunohistochemical images of 4-hydroxynonenal (4-HNE) in tumor tissue sections. Our comparison revealed a negative correlation between the reducing power of tumor tissue and the number of 4-HNE-positive cells. Furthermore, the control and IKE-treated groups exhibited significantly different distributions on the correlation map. Therefore, redox imaging using EPRI may contribute to the non-invasive detection of ferroptosis in vivo.
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spelling doaj-art-b18abdec1293472a95e6004c10d9d75e2025-01-21T15:12:48ZengTaylor & Francis GroupRedox Report1351-00021743-29282025-12-0130110.1080/13510002.2025.2454887Non-invasive electron paramagnetic resonance imaging detects tumor redox imbalance induced by ferroptosisKazuhiro Kato0Hironobu Yasui1Hideo Sato-Akaba2Miho C. Emoto3Hirotada G. Fujii4Maciej M. Kmiec5Periannan Kuppusamy6Masaki Nagane7Tadashi Yamashita8Osamu Inanami9Laboratory of Radiation Biology, Department of Applied Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, JapanLaboratory of Radiation Biology, Department of Applied Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, JapanDepartment of Electrical and Electronic Engineering, Graduate School of Integrated Science and Technology, Shizuoka University, Hamamatsu, JapanDepartment of Clinical Laboratory Science, School of Medical Technology, Health Sciences University of Hokkaido, Sapporo, JapanAdvanced Research Promotion Center, Health Sciences University of Hokkaido, Ishikari, JapanDepartments of Radiology and Radiation Oncology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USADepartments of Radiology and Radiation Oncology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USALaboratory of Biochemistry, School of Veterinary Medicine, Azabu University, Sagamihara, JapanLaboratory of Biochemistry, School of Veterinary Medicine, Azabu University, Sagamihara, JapanLaboratory of Radiation Biology, Department of Applied Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, JapanTargeting ferroptosis, cell death caused by the iron-dependent accumulation of lipid peroxides, and disruption of the redox balance are promising strategies in cancer therapy owing to the physiological characteristics of cancer cells. However, the detection of ferroptosis using in vivo imaging remains challenging. We previously reported that redox maps showing the reduction power per unit time of implanted tumor tissues via non-invasive redox imaging using a novel, compact, and portable electron paramagnetic resonance imaging (EPRI) device could be compared with tumor tissue sections. This study aimed to apply the EPRI technique to the in vivo detection of ferroptosis. Notably, redox maps reflecting changes in the redox status of tumors induced by the ferroptosis-inducing agent imidazole ketone erastin (IKE) were compared with the immunohistochemical images of 4-hydroxynonenal (4-HNE) in tumor tissue sections. Our comparison revealed a negative correlation between the reducing power of tumor tissue and the number of 4-HNE-positive cells. Furthermore, the control and IKE-treated groups exhibited significantly different distributions on the correlation map. Therefore, redox imaging using EPRI may contribute to the non-invasive detection of ferroptosis in vivo.https://www.tandfonline.com/doi/10.1080/13510002.2025.2454887Electron paramagnetic resonance imagingRedox imaging‌tumor redox statusferroptosiscancer therapy‌Imidazole ketone erastin
spellingShingle Kazuhiro Kato
Hironobu Yasui
Hideo Sato-Akaba
Miho C. Emoto
Hirotada G. Fujii
Maciej M. Kmiec
Periannan Kuppusamy
Masaki Nagane
Tadashi Yamashita
Osamu Inanami
Non-invasive electron paramagnetic resonance imaging detects tumor redox imbalance induced by ferroptosis
Redox Report
Electron paramagnetic resonance imaging
Redox imaging‌
tumor redox status
ferroptosis
cancer therapy
‌Imidazole ketone erastin
title Non-invasive electron paramagnetic resonance imaging detects tumor redox imbalance induced by ferroptosis
title_full Non-invasive electron paramagnetic resonance imaging detects tumor redox imbalance induced by ferroptosis
title_fullStr Non-invasive electron paramagnetic resonance imaging detects tumor redox imbalance induced by ferroptosis
title_full_unstemmed Non-invasive electron paramagnetic resonance imaging detects tumor redox imbalance induced by ferroptosis
title_short Non-invasive electron paramagnetic resonance imaging detects tumor redox imbalance induced by ferroptosis
title_sort non invasive electron paramagnetic resonance imaging detects tumor redox imbalance induced by ferroptosis
topic Electron paramagnetic resonance imaging
Redox imaging‌
tumor redox status
ferroptosis
cancer therapy
‌Imidazole ketone erastin
url https://www.tandfonline.com/doi/10.1080/13510002.2025.2454887
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