Dynamic in vivo oxymetry using overhauser enhanced MR imaging

Golman, Klaes; Js, Petersson; Ardenkjaer-Larsen, JH; Leunbach, Ib; Lg, Wistrand; Ehnholm, Gösta; K, Liu

doi:10.1002/1522-2586(200012)12:6<929::aid-jmri17>3.0.co;2-j

Cited by 102 publications

(110 citation statements)

References 41 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…PTM-TE was soluble in organic solvents such as chloroform, n-hexane, n-octanol, methanol, and mineral oil. The ESR spectra of PTM-TE dissolved in these solvents were composed of narrow singlet line with a small satellite doublet signal that originated from 13 C nuclei (Figs. 3a, b), in accordance with the ESR spectrum in the literature in which PTM-TE had been dissolved in dimethylsulfoxide.…”

Section: Esr Spectra Of Ptm-te Incorporated In Liposomal Membranessupporting

confidence: 89%

“…1b), and the spectrum showed an apparently broad singlet line (DH msl ϭ0.444 mT). This suggests that the shoulder is not mainly originated from 13 C nuclei, but rather from 12 C-PTM-TE in the state other than that of the radical giving a narrow signal.…”

Section: Esr Spectra Of Ptm-te Incorporated In Liposomal Membranesmentioning

confidence: 99%

“…Toxicities of the radicals were reportedly low (LD 50 , 8 mmol/kg in mice). 13) Therefore, they have been injected intravenously into experimental animals, and in vivo oxygen maps have been imaged with OMRI 14) and ESR imaging. 15) Furthermore, water-soluble trityl radicals were also utilized as probes of superoxide generation 12) and pH 16) for ESR spectroscopy and its imaging.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Effect of Cholesterol on Distribution of Stable, Hydrophobic Perchlorotriphenylmethyl Triethylester Radical Incorporated in Lecithin Liposomal Membranes

Takeshita

Okazaki

Kansui

2011

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Along with the development and improvement of in vivo magnetic resonance imaging systems such as ESR imaging system and Overhauser enhanced magnetic resonance imaging (OMRI) system, durable organic radicals have been used as imaging agents to probe various physiological status and to trace drugs with these imaging systems. The paramagnetism of durable nitroxyl radicals responds to their redox reactions, and some of them are commercially available. For these reasons, nitroxyl radicals have been conventionally used as labels of drug carriers and probes for in vivo redox status including the generation of reactive oxygen species. 1-7) However, the disadvantage of nitroxyl radicals is the loss of their paramagnetism by enzymatic and nonenzymatic reduction in the body. [8][9][10][11] Triphenylmethyl radicals (trityl radicals) are another family of durable organic radicals. These radicals are resistant to various reducing and oxidizing agents such as ascorbic acid, glutathione, hydrogen peroxide, and iron. 12) Some water-soluble trityl radicals such as Oxo63 gave a long ESR relaxation time giving a singlet, a very narrow ESR signal, and the relaxation time relating to the line width was sensitive to the partial pressure of oxygen. Toxicities of the radicals were reportedly low (LD 50 , 8 mmol/kg in mice). 13) Therefore, they have been injected intravenously into experimental animals, and in vivo oxygen maps have been imaged with OMRI 14) and ESR imaging. 15) Furthermore, water-soluble trityl radicals were also utilized as probes of superoxide generation 12) and pH 16) for ESR spectroscopy and its imaging. In contrast to hydrophilic trityl radicals, only a few reports have described the application of hydrophobic ones. Although perchlorotriphenylmethyl triethylester radical (PTM-TE; Chart 1), one of the hydrophobic trityl radicals, also showed a singlet ESR signal, its oxygen response was solvent-dependent. 17) The oxygen response of its ESR line width was high in a highly hydrophobic environment. Therefore, the radical was doped in oxygen-permeable resin chips made of polydimethyl siloxane 18) or encapsulated into microspheres of hexamethyldisiloxane. 19) For the hydrophobic property and stability of PTM-TE, this radical is a potential label to trace drug carriers such as liposomes and lipid microspheres in live animals without using a radioisotope. In order to use PTM-TE as a label of liposomes, knowledge about its manner of incorporation into liposomal membranes is necessary. In this study, multilamellar liposomes composed of either egg yolk phosphatidylcholine (egg-PC) or egg-PC and cholesterol were prepared with PTM-TE. The lateral distribution of PTM-TE in the membranes and the effect of cholesterol on the distribution were analyzed with ESR spectroscopy. ExperimentalReagents PTM-TE was synthesized in our laboratory following methods reported in the literature. Perchlorotriphenylmethyl triethylester radical (PTM-TE) is a hydrophobic, stable radical giving a narrow singlet ESR signal with a small satellite signal...

show abstract

Section: Esr Spectra Of Ptm-te Incorporated In Liposomal Membranessupporting

confidence: 89%

Section: Esr Spectra Of Ptm-te Incorporated In Liposomal Membranesmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Effect of Cholesterol on Distribution of Stable, Hydrophobic Perchlorotriphenylmethyl Triethylester Radical Incorporated in Lecithin Liposomal Membranes

Takeshita

Okazaki

Kansui

2011

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

show abstract

“…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. [161][162][163] In human blood, the stability of triarylmethyl radicals varies from a half-life of a few hours to one of more than 24 h depending on the particular structure of the compound. These compounds were first developed by Nycomed innovation.…”

Section: Soluble Paramagnetic Materialsmentioning

confidence: 99%

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

2004

View full text Add to dashboard Cite

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.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Dynamic in vivo oxymetry using overhauser enhanced MR imaging

Cited by 102 publications

References 41 publications

Effect of Cholesterol on Distribution of Stable, Hydrophobic Perchlorotriphenylmethyl Triethylester Radical Incorporated in Lecithin Liposomal Membranes

Effect of Cholesterol on Distribution of Stable, Hydrophobic Perchlorotriphenylmethyl Triethylester Radical Incorporated in Lecithin Liposomal Membranes

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

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

Contact Info

Product

Resources

About