In vivo temporal EPR imaging of the brain of rats by using two types of blood-brain barrier-permeable nitroxide radicals

Yokoyama, Hidekastu; Itoh, Osamu; Aoyama, Mikio; Obara, Heitaro; Ohya, Hiroaki; Kamada, Hitoshi

doi:10.1016/s0730-725x(02)00491-5

Cited by 40 publications

(33 citation statements)

References 14 publications

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“…3-Carboxy-PROXYL was purchased from Sigma. 3-Hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-Noxyl (HM-PROXYL) was synthesized from 3-carboxy-PROXYL following the methods of Yokoyama and colleagues (22). Paramagnetic LiPc was synthesized electrochemically as previously reported (23,24).…”

Section: Methodsmentioning

confidence: 99%

Heterogeneity of Regional Redox Status and Relation of the Redox Status to Oxygenation in a Tumor Model, Evaluated Using Electron Paramagnetic Resonance Imaging

et al. 2010

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It is widely accepted that redox status, along with the partial pressure of oxygen (pO 2 ), determines the efficacy of some therapeutic methods applied to treat tumors, including radiation. Redox status, evaluated by the reduction of a nitroxyl probe, was reportedly heterogeneous in a mouse tumor model. However, neither variation of heterogeneity of the redox status among mice nor the relation of the redox status to pO 2 in tumors has been characterized sufficiently. In this study, the regional reduction status in a mouse radiation-induced fibrosarcoma tumor model was evaluated using sequential three-dimensional electron paramagnetic resonance (EPR) imaging after i.v. injection of a tissue-permeable nitroxyl probe, HM-PROXYL. The regional decay of HM-PROXYL signal obeyed first-order kinetics, and the amplitude of the reduction rate and extent of its heterogeneity in a tumor varied among six mice. The tissue pO 2 was measured using EPR oximetry with lithium phthalocyanine (LiPc) microcrystals implanted within the tumor. The location of LiPc was determined with EPR imaging. A sequential image was obtained following the injection of HM-PROXYL, even after LiPc implantation, by choosing an HM-PROXYL signal peak which does not overlap with the signal of LiPc. The relationship between pO 2 and the reduction rate at the region of pO 2 measurement was found to be low (r = 0.357) in 13 tumor-bearing mice, indicating that the extent of oxygenation does not necessarily affect the redox status under air-breathing conditions. The results strongly indicate the necessity of measurements of both redox status and oxygenation in every tumor to characterize tumor physiology. Cancer Res; 70(10); 4133-40. ©2010 AACR.

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Section: Methodsmentioning

confidence: 99%

Heterogeneity of Regional Redox Status and Relation of the Redox Status to Oxygenation in a Tumor Model, Evaluated Using Electron Paramagnetic Resonance Imaging

et al. 2010

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“…The hydroxymethyl-PROXYL was synthesized at our institute (9,10). The phantoms at various oxygen concentrations were prepared by bubbling different oxygen/nitrogen gas mixtures (obtained with a gas blender, GB-3660; Kofloc Co., Japan) through the solution for 60 min.…”

Section: Phantommentioning

confidence: 99%

Noninvasive in vivo determination of intracerebral oxygen concentration in rats by a longitudinally detected ESR (LODESR) technique

Yokoyama

Sato

Fukui

et al. 2004

Magnetic Resonance in Med

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“…The 700 MHz radio-frequency (RF) EPR spectrometer constructed at our laboratory has been described in detail [1][2][3]. It consists of an EPR resonator, a main electromagnet, a pair of field scan coils, a pair of field gradient coils, a pair of field modulation coils, power supplies, a personal computer, 700 MHz RF circuits for homodyne detection, and intermediate-frequency circuits for lock-in detection at a fietd modulation frequency of 100 kHz.…”

Section: Epr Spectrometermentioning

confidence: 99%

“…Temporal electron paramagnetic resonance (EPR) imaging of the brain of rats that received a nitroxide radical permeating the blood-brain barrier was made to estimate the cerebral reducing ability on the basis of nitroxide reduction [1][2][3]. A nitroxide radical is reduced by a reducing agent (such as ascorbic acid) to an EPR-silent compound, hydroxylamine [1,3].…”

Section: Introductionmentioning

confidence: 99%

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Reaction kinetics analysis to estimate in vivo decay rate of EPR signals of a nitroxide radical in the brain and the inferior vena cava of rats

et al. 2003

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To clarify the degree of the influence of the peripheral organs on the temporal changes in the electron paramagnetic resonance (EPR) signal intensity of a nitroxide radical permeating the bloodbrain barrier, 3-hydroxymethyl-2,2,5,5-tetramethylprrotidine-l-oxyl (hydroxymethyl-PROXYL), in the brain, temporal changes in the EPR signal in the brain or inferior vena cava of rats were measured by an in vivo 700 MHz radio-frequency EPR spectrometer equipped with a bridged loop-gap resonator ora surface-coil-type resonator. In all measurements, good linearity was observed on semilogarithmic plots of the signal intensity against time after the hydroxymethyl-PROXYL injection. From these plots, the reaction rate and the initial level of hydroxymethyl-PROXYL in the brain and the vena cava were calculated. A mathematical model expressing the nitroxide radical concentration in the brain, which is connected to other organs via the circulatory system, was made. With this model and the results of the EPR measurements, the degrees of influence of the nitroxide reduction in the brain and the other organs were simulated. It was found that the reaction rate (equal to log2/halflife) of hydroxymethyl-PROXYL observed in the brain reflected the reduction of hydroxymethyl-PROXYL there and was not influenced by the reduction in other organs.

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In vivo temporal EPR imaging of the brain of rats by using two types of blood-brain barrier-permeable nitroxide radicals

Cited by 40 publications

References 14 publications

Heterogeneity of Regional Redox Status and Relation of the Redox Status to Oxygenation in a Tumor Model, Evaluated Using Electron Paramagnetic Resonance Imaging

Heterogeneity of Regional Redox Status and Relation of the Redox Status to Oxygenation in a Tumor Model, Evaluated Using Electron Paramagnetic Resonance Imaging

Noninvasive in vivo determination of intracerebral oxygen concentration in rats by a longitudinally detected ESR (LODESR) technique

Reaction kinetics analysis to estimate in vivo decay rate of EPR signals of a nitroxide radical in the brain and the inferior vena cava of rats

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