Sense and Sensibility of Oxygen in Pathophysiology Using EPR Oximetry

Kuppusamy, Periannan

doi:10.1007/978-3-030-47318-1_9

Cited by 4 publications

(4 citation statements)

References 239 publications

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“…Finally, as this paper is submitted for the special issue of Molecules on "Application of EPR Spectroscopy in Biophysics and Biochemistry", we believe that the present study well illustrates the potential role of EPR in trying to identify new pharmacological treatments that may help in fighting cancer. While the final results obtained here are rather disappointing in terms of the potentiation of radiation sensitivity, there are many other examples for which EPR has been instrumental in characterizing the effect of potential treatments [47][48][49][50][51].…”

Section: Discussionmentioning

confidence: 73%

EPR Investigations to Study the Impact of Mito-Metformin on the Mitochondrial Function of Prostate Cancer Cells

et al. 2022

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Background: Mito-metformin10 (MM10), synthesized by attaching a triphenylphosphonium cationic moiety via a 10-carbon aliphatic side chain to metformin, is a mitochondria-targeted analog of metformin that was recently demonstrated to alter mitochondrial function and proliferation in pancreatic ductal adenocarcinoma. Here, we hypothesized that this compound may decrease the oxygen consumption rate (OCR) in prostate cancer cells, increase the level of mitochondrial ROS, alleviate tumor hypoxia, and radiosensitize tumors. Methods: OCR and mitochondrial superoxide production were assessed by EPR (9 GHz) in vitro in PC-3 and DU-145 prostate cancer cells. Reduced and oxidized glutathione were assessed before and after MM10 exposure. Tumor oxygenation was measured in vivo using 1 GHz EPR oximetry in PC-3 tumor model. Tumors were irradiated at the time of maximal reoxygenation. Results: 24-hours exposure to MM10 significantly decreased the OCR of PC-3 and DU-145 cancer cells. An increase in mitochondrial superoxide levels was observed in PC-3 but not in DU-145 cancer cells, an observation consistent with the differences observed in glutathione levels in both cancer cell lines. In vivo, the tumor oxygenation significantly increased in the PC-3 model (daily injection of 2 mg/kg MM10) 48 and 72 h after initiation of the treatment. Despite the significant effect on tumor hypoxia, MM10 combined to irradiation did not increase the tumor growth delay compared to the irradiation alone. Conclusions: MM10 altered the OCR in prostate cancer cells. The effect of MM10 on the superoxide level was dependent on the antioxidant capacity of cell line. In vivo, MM10 alleviated tumor hypoxia, yet without consequence in terms of response to irradiation.

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Section: Discussionmentioning

confidence: 73%

EPR Investigations to Study the Impact of Mito-Metformin on the Mitochondrial Function of Prostate Cancer Cells

et al. 2022

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“…Other lithium derivatives have been tested, and LiNc-BuO was chosen because of its high spin density, oxygen sensitivity in a wide range, and resistance to many chemical and physical factors [ 9 , 10 ]. LiNc-BuO in PDMS, denoted Oxychip, has been used in many animal models and in patients to study oxygenation in the skin and tumors [ 11 – 14 ]. We have decided to use an Oxychip implanted in tumor tissue for non-invasive, fast, precise, and repeatable oximetry during therapy.…”

Section: Introductionmentioning

confidence: 99%

Pulse and CW EPR Oximetry Using Oxychip in Gemcitabine-Treated Murine Pancreatic Tumors

Dziurman,

Drzał,

Murzyn

et al. 2023

Mol Imaging Biol

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Purpose The goal of this work was to compare pO2 measured using both continuous wave (CW) and pulse electron paramagnetic resonance (EPR) spectroscopy. The Oxychip particle spin probe enabled longitudinal monitoring of pO2 in murine pancreatic tumor treated with gemcitabine during the course of therapy. Procedures Pancreatic PanO2 tumors were growing in the syngeneic mice, in the leg. Five doses of saline in control animals or gemcitabine were administered every 3 days, and pO2 was measured after each dose at several time points. Oxygen partial pressure was determined from the linewidth of the CW EPR signal (Bruker E540L) or from the T2 measured using the electron spin echo sequence (Jiva-25™). Results The oxygen sensitivity was determined from a calibration curve as 6.1 mG/mm Hg in CW EPR and 68.5 ms−1/mm Hg in pulse EPR. A slight increase in pO2 of up to 20 mm Hg was observed after the third dose of gemcitabine compared to the control. The maximum delta pO2 during the therapy correlated with better survival. Conclusions Both techniques offer fast and reliable oximetry in vivo, allowing to follow the effects of pharmaceutic intervention.

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“…Such reporters will be necessary in the case of vessel normalization attempts aiming to assess which vessel normalization protocols are valid to design efficient adjuvant therapies. Indeed a punctual but stable sensor of oxygen partial pressure in the tumor site is a tool to follow the efficacy of an antihypoxic treatment along the various protocols of its administration [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Oxygen therapeutic window induced by myo-inositol trispyrophosphate (ITPP)–Local pO2 study in murine tumors

et al. 2023

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Hypoxia, an inevitable feature of locally advanced solid tumors, has been known as an adverse prognostic factor, a driver of an aggressive phenotype, and an unfavorable factor in therapies. Myo-inositol trispyrophosphate (ITPP) is a hemoglobin modifier known to both increase O2 release and normalize microvasculature. Our goal was to measure the tumor oxygen partial pressure dynamic changes and timing of the therapeutic window after ITPP systemic administration. Two syngeneic tumor models in mice, B16 melanoma and 4T1 breast carcinoma, were used, with varying ITPP dose schedules. Tissue oxygenation level was measured over several days in situ in live animals by Electron Paramagnetic Resonance oximetry with implanted OxyChip used as a constant sensor of the local pO2 value. Both B16 and 4T1 tumors became more normoxic after ITPP treatment, with pO2 levels elevated by 10–20 mm Hg compared to the control. The increase in pO2 was either transient or sustained, and the underlying mechanism relied on shifting hypoxic tumor areas to normoxia. The effect depended on ITPP delivery intervals regarding the tumor type and growth rate. Moreover, hypoxic tumors before treatment responded better than normoxic ones. In conclusion, the ITPP-generated oxygen therapeutic window may be valuable for anti-tumor therapies requiring oxygen, such as radio-, photo- or immunotherapy. Furthermore, such a combinatory treatment can be especially beneficial for hypoxic tumors.

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Sense and Sensibility of Oxygen in Pathophysiology Using EPR Oximetry

Cited by 4 publications

References 239 publications

EPR Investigations to Study the Impact of Mito-Metformin on the Mitochondrial Function of Prostate Cancer Cells

EPR Investigations to Study the Impact of Mito-Metformin on the Mitochondrial Function of Prostate Cancer Cells

Pulse and CW EPR Oximetry Using Oxychip in Gemcitabine-Treated Murine Pancreatic Tumors

Oxygen therapeutic window induced by myo-inositol trispyrophosphate (ITPP)–Local pO2 study in murine tumors

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