Use of nitroxides for assessing perfusion, oxygenation, and viability of tissues: <i>In vivo</i> EPR and MRI studies

Gallez, Bernard; Bačić, Goran; Goda, Fuminori; Jiang, Jun; O’Hara, Julia A.; Dunn, Jeff F.; Swartz, Harold M.

doi:10.1002/mrm.1910350113

Cited by 89 publications

(70 citation statements)

References 29 publications

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“…Several interesting studies analyzing the pharmacokinetics of paramagnetic compounds were obtained in mice by putting the tail of the animals directly in the EPR resonator. 118,119 As the tail veins of mice are superficial, a non-invasive monitoring of the concentration of paramagnetic compounds was achievable with high sensitivity and short time resolution between sampling. Larger aqueous samples or animals can be studied only by reducing the operating frequency to 1 GHz or less, but this results in a reduced sensitivity.…”

Section: Frequency/magnetic Field Ratiomentioning

confidence: 99%

“…For most nitroxides, the linewidth in the absence of oxygen is approximately 1 Gauss. To increase the sensitivity to oxygen, it is convenient to use perdeuterated nitroxides, 119,135 for which the linewidth is lower than 200 mGauss. It is also possible to use nitroxides with a resolved superhyperfine structure to increase sensitivity to oxygen.…”

Section: Soluble Paramagnetic Materialsmentioning

confidence: 99%

“…154,155 Special care should be taken when linking the signal decay of nitroxides to the redox state, because the kinetics of clearance also depend on the perfusion (and wash-out from the tissue) and on the viability of cells. 119 The recent development of triarylmethyl radicals (Fig. 4) has significantly expanded the potential for using oxygen-sensitive free radicals in EPR, [156][157][158] EPR imaging 128,159,160 and related techniques such as dynamic nuclear polarization.…”

Section: Soluble Paramagnetic Materialsmentioning

confidence: 99%

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Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

2004

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This review paper attempts to provide an overview of the principles and techniques that are often termed electron paramagnetic resonance (EPR) oximetry. The paper discusses the potential of such methods and illustrates they have been successfully applied to measure oxygen tension, an essential parameter of the tumor microenvironment. To help the reader understand the motivation for carrying out these measurements, the importance of tumor hypoxia is first discussed: the basic issues of why a tumor is hypoxic, why these hypoxic microenvironments promote processes driving malignant progression and why hypoxia dramatically influences the response of tumors to cytotoxic treatments will be explained. The different methods that have been used to estimate the oxygenation in tumors will be reviewed. To introduce the basics of EPR oximetry, the specificity of in vivo EPR will be discussed by comparing this technique with NMR and MRI. The different types of paramagnetic oxygen sensors will be presented, as well as the methods for recording the information (EPR spectroscopy, EPR imaging, dynamic nuclear polarization). Several applications of EPR for characterizing tumor oxygenation will be illustrated, with a special emphasis on pharmacological interventions that modulate the tumor microenvironment. Finally, the challenges for transposing the method into the clinic will also be discussed.

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Section: Frequency/magnetic Field Ratiomentioning

confidence: 99%

Section: Soluble Paramagnetic Materialsmentioning

confidence: 99%

Section: Soluble Paramagnetic Materialsmentioning

confidence: 99%

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Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

2004

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“…Though the use of nitroxide as a T 1 -enhancing MRI contrast agent was realized early [20][21][22][23], the bio-reduction and rapid clearance have made them less useful than the metal-based Gd 3+ complex contrast agents [24;25], which had a long biological half life and high molar relaxivity, compared with the single, odd-electron containing nitroxides. However, the bioreduction of nitroxides can be monitored to effectively probe the redox status of tissues [4; 26].…”

Section: Introductionmentioning

confidence: 99%

Monitoring redox-sensitive paramagnetic contrast agent by EPRI, OMRI and MRI

Hyodo

Murugesan

Matsumoto

et al. 2008

Journal of Magnetic Resonance

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A comparative study of tissue redox-status imaging using commonly used redox sensitive nitroxides has been carried out using electron paramagnetic resonance imaging (EPRI), Overhauser magnetic resonance imaging (OMRI) and conventional T 1 -weighted magnetic resonance imaging, MRI. Imaging studies using phantoms of different nitroxides at different concentration levels showed that EPRI and OMRI sensitivities were found to be linearly dependent on line width of nitroxides up to 2 mM, and the enhancement in MRI intensity was linear up to 5 mM. The sensitivity and resolution of EPRI and OMRI images depended significantly on the line width of the nitroxides whereas the MRI images were almost independent of EPR line width.Reduction of the paramagnetic 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (3CP) by ascorbic acid (AsA) to the diamagnetic by hydroxylamine was monitored from a sequence of temporal images, acquired using the three imaging modalities. The decay rates determined by all the three modalities were found to be similar. However the results suggest that T 1 weighted MRI can monitor the redox status, in addition to providing detailed anatomical structure in a short time. Therefore, a combination of MRI with nitroxides as metabolically responsive contrast agents can be a useful technique for the in vivo imaging probing tissue redox status.

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“…Two kinds of paramagnetic materials can be used: particulate materials and soluble materials such as nitroxides or trityl radicals. [9][10][11][12] Particulate materials are usually inert and possess a higher sensitivity for oxygen than soluble materials. Once particulate materials are implanted in tissue, it is possible to make repeated localized measurements over long periods of time.…”

Section: Introductionmentioning

confidence: 99%

Development and evaluation of biocompatible inks for the local measurement of oxygen using in vivo EPR

2004

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In vivo EPR oximetry is a powerful minimally invasive method that allows the measurement of oxygen in tissues through the use of a paramagnetic probe. In the present study, we investigated new strategies for preparing biocompatible inks containing carbon black particles (Printex U), which could be used as oxygen sensors. The carbon black particles were dispersed in solutions of biocompatible polymers of carboxy methyl cellulose (CMC), hydroxypropyl methyl cellulose (HPMC) or polyvinyl pyrrolidone (PVP). A total of 12 polymers with different molecular weights were tested. A physico-chemical characterization of the inks was carried out to assess the sedimentation of the particles, the rheological behavior of these inks, and the relative diffusion of the inks. The preparations with CMC and PVP had the highest viscosity and stability. The presence of the polymers did not modify the calibration curves (EPR linewidth as a function of the pO 2 ) of the carbon black. In vivo, the oxygen sensors were stable for at least one month in muscles as the EPR linewidth remained fully sensitive to induced ischemia or carbogen challenge. The calibration curve was not modified after this period of implantation. A first study of biocompatibility was carried out in vitro (hemolysis and cytotoxicity assay) and in vivo (histological examination). No sign of toxicity was observed using these inks. These preparations are good candidates for future in vivo studies including clinical trials.

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Use of nitroxides for assessing perfusion, oxygenation, and viability of tissues: In vivo EPR and MRI studies

Cited by 89 publications

References 29 publications

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

Monitoring redox-sensitive paramagnetic contrast agent by EPRI, OMRI and MRI

Development and evaluation of biocompatible inks for the local measurement of oxygen using in vivo EPR

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