@misc{oai:repo.qst.go.jp:00071292,
 author = {Bakalova-Zheleva, Rumiana and Zhelev, Zhivko and Kokuryo, Daisuke and Aoki, Ichio and Veselina, Gadjeva and Saga, Tsuneo and バカロバ ルミアナ and Ｚｈｅｌｅｖ Ｚｈｉｖｋｏ and 國領 大介 and 青木 伊知男 and 佐賀 恒夫},
 month = {Sep},
 note = {Background: Redox signalling is crucial for carcinogenesis and tissue redox activity has emerged as an important sensing platform for cancer diagnosis and planning of therapeutic strategy. The cells and tissues of healthy mammals are characterized by low level of reactive oxygen species (ROS) and some constant (reference) level of reducing equivalents. Increasing of ROS above the critical level provokes genomic instability and uncontrolled proliferation, which causes normal cells to become malignant. The present study aimed to clarify the dynamics of tissue redox activity (TRA) in cancer progression and assess the importance of this parameter for therapeutic strategies.
Methods: The experiments were conducted on brain tissues of neuroblastoma-bearing, glioma-bearing and healthy mice. TRA was visualized in vivo by nitroxide-enhanced magnetic resonance imaging (MRI) on anesthetized animals or in vitro by electron paramagnetic resonance (EPR) spectroscopy on isolated tissue specimens. Two biochemical parameters were analyzed in parallel: tissue total antioxidant capacity (TTAC) and plasma levels of matrix metalloproteinases (MMPs). 
Results: In the early stage of cancer, the brain tissues were characterized by a shorter-lived MRI signal than that from healthy brains (indicating a higher reducing activity for the nitroxide radical), which was accompanied by an enhancement of TTAC and MMP9 plasma levels. In the terminal stage of cancer, tissues in both hemispheres were characterized by a longer-lived MRI signal than in healthy brains (indicating a high oxidative activity) that was accompanied by a decrease in TTAC and an increase in the MMP2/MMP9 plasma levels. Cancer progression also affected the redox potential of tissues distant from the primary tumor locus (liver and lung). Their oxidative status increased in both stages of cancer.
Conclusions: This study demonstrates that tissue redox balance is very sensitive to cancer development and can be used as a diagnostic marker of carcinogenesis. The method is simple and applicable on isolated tissue and blood specimens. The method demonstrates the potential for promising application in molecular imaging diagnostic in vivo on humans following the development of cell-penetrating nitroxide probes with high contrast, low toxicity and minimal side effects. The most important observations are that the oxidative status of noncancerous tissues (even those distant from the primary tumor locus) increases with cancer progression and that these tissues become susceptible to oxidative stress and damage., 2013 World Molecular Imaging Congress},
 title = {Imaging of Tissue Redox Activity from Early to Terminal Stage of Cancer Development Using Nitroxide-enhanced MRI},
 year = {2013}
}