Comparisons of EPR imaging and T1-weighted MRI for efficient imaging of nitroxyl contrast agents

Matsumoto, Ken‐ichiro; Narazaki, Michiko; Ikehira, Hiroo; Anzai, Kazunori; Ikota, Nobuo

doi:10.1016/j.jmr.2007.03.013

Cited by 12 publications

(7 citation statements)

References 23 publications

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“…To approve this assumption, we used carbamoyl-PROXYL. Carbamoyl-PROXYL is a pyrrolidine derivative, which is characterized with high water-solubility and low permeability for cell membranes (Matsumoto et al , 2007. We observed that the time-decay of EPR signal of carbamoyl-PROXYL in the bloodstream was much slower than for other nitroxyls (TEMPOL, SLENU, SLCNUgly), presumably, as a result of slower transportation of this compound to the cells and tissues.…”

Section: Resultsmentioning

confidence: 88%

“…The hydrophobic nitroxyls SLENU and SLCNUgly will characterize by fast and tight incorporation in cell membranes, while the hydrophilic TEMPOL will exist predominantly in the aqueous phase of the blood, moving freely and easily. In EPR data analysis of nitroxyl radicals, the variations in Line 3 in the triplet of EPR spectrum (and especially Line 2/Line 3 amplitude ratio) is considered as an indicator for the motion of nitroxyl radical (Matsumoto et al 2007). If the ratio increases, the motion decreases.…”

Section: Resultsmentioning

confidence: 99%

“…Using EPR imaging, a very good correlation has been found between the level of oxygen and rate constant of nitroxyl reduction, as well as between the level of reducing equivalents and rate constant of nitroxyl oxidation (Matsumoto et al 2007;Hyodo et al 2008). Thus, the balance between the reduction activity of biological fluids or tissues and local oxidation reactions determines the rate of EPR signal decay of nitroxyl radical.…”

Section: Introductionmentioning

confidence: 97%

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EPR signal reduction kinetic of several nitroxyl derivatives in blood in vitro and in vivo

Zhelev¹,

Matsumoto²,

Gadjeva³

et al. 2009

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Abstract. The present study is focused on the mechanism(s) of electron-paramagnetic resonance (EPR) signal reduction kinetic of several nitroxyl radicals and nitroxyl-labeled anticancer drugs in physiological solutions in the context of their application for evaluation of oxidation/reduction status of blood and tissues -an important step in biomedical diagnostics and planning of therapy of many diseases. The nitroxyl derivatives were characterized with different size and water-solubility. Some of them are originally synthesized. In buffer, in the absence of reducing and oxidizing equivalents, the EPR signal intensity of all nitroxyls was constant with the time. In serum and cell cultured medium, in an absence of cells and in a negligible amount of reducing and oxidizing equivalents, there was no significant EPR signal reduction, too. In vitro (in freshly isolated blood samples), the EPR signal intensity was characterized with slow decrease within 30 min, presumably as a result of interaction between the nitroxyl derivative and blood cells. The EPR spectrum of hydrophobic nitroxyls showed a slight anisotropy in cell-containing solutions and it did not changed in non-cell physiological solutions. This suggests for a limited motion of more hydrophobic nitroxyls through their preferable location in cell membranes. In vivo (in the bloodstream of mice under anesthesia), the EPR signal reduction kinetic was characterized by two phases: i) a rapid enhancement within 30 s as a result of increasing of nitroxyl concentration in the bloodstream after its intravenous injection, followed by ii) a rapid decrease (~80-100%) within 2-5 min, presumably as a result of transportation of nitroxyl in the tissues. The hydrophobic nitroxyls were characterized with stronger and faster decrease in EPR signal intensity in the blood in vivo, as a result of their higher cell permeability, rapid clearance from the bloodstream and/or transportation in the surrounding tissues. The hydrophilic nitroxyls persist in the bloodstream (in their radical form) for a comparatively long time.The data suggest that the hydrophobic cell-permeable nitroxyl derivatives are most appropriate for evaluation of cell and tissue oxidation/reduction status, while the hydrophilic nitroxyls (impermeable for cell membranes or with very slow cell permeability) are most appropriate for evaluation of oxidation/reduction status of blood using EPR imaging.

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Section: Resultsmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

EPR signal reduction kinetic of several nitroxyl derivatives in blood in vitro and in vivo

Zhelev¹,

Matsumoto²,

Gadjeva³

et al. 2009

gpb

View full text Add to dashboard Cite

show abstract

“…However, the good linear relationship between the T 1 contrast enhancement and the concentration of nitroxyl groups increases the significance of our nanoemulsions for biomedical application . Furthermore, it is a big advantage that nitroxide radicals can act as T 1 ‐enhancing MRI contrast agents with much‐lower toxicity than the commonly used molecular Gd III ‐complexes …”

Section: Resultsmentioning

confidence: 99%

Preparation of Robust Metal‐Free Magnetic Nanoemulsions Encapsulating Low‐Molecular‐Weight Nitroxide Radicals and Hydrophobic Drugs Directed Toward MRI‐Visible Targeted Delivery

Nagura

Takemoto

Moronaga

et al. 2017

Chemistry A European J

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With a view to developing a theranostic nanomedicine for targeted drug delivery systems visible by magnetic resonance (MR) imaging, robust metal-free magnetic nanoemulsions (mean particle size less than 20 nm) consisting of a biocompatible surfactant and hydrophobic, low molecular weight 2,2,5-trimethyl-5-(4-alkoxy)phenylpyrrolidine-N-oxyl radicals were prepared in pH 7.4 phosphate-buffered saline (PBS). The structure of the nanoemulsions was characterized by electron paramagnetic resonance spectroscopy, and dynamic light scattering and small-angle neutron-scattering measurements. The nanoemulsions showed high colloidal stability, low cytotoxicity, enough reduction resistance to excess ascorbic acid, and sufficient contrast enhancement in the proton longitudinal relaxation time (T ) weighted MR images in PBS in vitro (and preliminarily in vivo). Furthermore, the hydrophobic anticancer drug paclitaxel could be encapsulated inside the nanoparticles, and the resulting paclitaxel-loaded nanoemulsions were efficiently incorporated into HeLa cells to suppress cell growth.

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“…Therefore, image enhancement in tissue with a given T 1 should depend on the nitroxide concentration (Figure 4). On the other hand, image enhancement is affected by change of spectral shape and height in EPRI in addition to the concentration (Figure 4) (Matsumoto et al 2007). The near-independence of the relaxivity on the nature of nitroxide makes it easy to compare tissue redox status by MRI, whereas in EPRI, the line width and spectral multiplicity determines the image quality in terms of resolution and dynamic range.…”

Section: Nitroxides As Mri Redox Active Contrast Agentsmentioning

confidence: 99%

Assessment of tissue redox status using metabolic responsive contrast agents and magnetic resonance imaging

Hyodo

Soule

Matsumoto

et al. 2008

Journal of Pharmacy and Pharmacology

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Regulation of tissue redox status is important to maintain normal physiological conditions in the living body. Disruption of redox homeostasis may lead to oxidative stress and can induce many pathological conditions such as cancer, neurological disorders, and aging. Therefore, imaging of tissue redox status could have clinical applications. Redox imaging employing magnetic resonance imaging (MRI) with nitroxides as cell permeable redox sensitive contrast agents has been used for non-invasive monitoring of tissue redox status in animal models. The redox imaging applications of nitroxide EPRI and MRI are reviewed here, with a focus on application of tumor redox status monitoring. While particular emphasis has been placed on differences in the redox status in tumors compared selected normal tissues, the technique possesses the potential to have broad applications to the study of other disease states, inflammatory processes, and other circumstances where oxidative stress is implicated.

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Comparisons of EPR imaging and T1-weighted MRI for efficient imaging of nitroxyl contrast agents

Cited by 12 publications

References 23 publications

EPR signal reduction kinetic of several nitroxyl derivatives in blood in vitro and in vivo

EPR signal reduction kinetic of several nitroxyl derivatives in blood in vitro and in vivo

Preparation of Robust Metal‐Free Magnetic Nanoemulsions Encapsulating Low‐Molecular‐Weight Nitroxide Radicals and Hydrophobic Drugs Directed Toward MRI‐Visible Targeted Delivery

Assessment of tissue redox status using metabolic responsive contrast agents and magnetic resonance imaging

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