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Query: UNIPROT:O14944 (EPR)
 13,097 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have conjugated bovine serum albumin (BSA) with a pyrrolidinyl nitroxide and report on the in vivo pharmacokinetic properties of this conjugate in mice. In vivo EPR measurements of nitroxide were obtained after intravenous injection of 30 mg of labeled BSA by analysis of the nitroxide signal from the tails of mice. Following in vivo nitroxide measurements, the animals were sacrificed by exsanguination and organs were removed for determination of nitroxide levels. The level of nitroxide as determined by in vivo measurements declined exponentially with time and had a half-life (t1/2) of 7 hours. Blood nitroxide levels also declined exponentially with time with an initial t1/2 of 70 minutes and a terminal t1/2 of 10 hours. Nitroxide concentration varied among different organs; no nitroxide was detected within brain whereas lung had high concentrations of nitroxide. Liver and kidney both had relatively low levels of oxidized nitroxide, though total nitroxide (reduced plus oxidized) accumulated in the kidneys with time. Nitroxide-labeled BSA was well tolerated by the mice, is relatively stable, and is mainly confined to the intravascular space. Nitroxide-labeled albumin may be useful as a contrast agent for MRI or EPR imaging.
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PMID:Pharmacokinetic properties of nitroxide-labeled albumin in mice. 820 58

The effects of fusinite, a new agent for the measurement of the concentration of oxygen in vivo by EPR, on MRI images have been studied. There was little effect on spin-echo T1-weighted images, but the fusinite resulted in large effects on T2-weighted images. Especially large effects could be observed when using spoiled gradient echo sequences (SPGR). The observed measurements of oxygen by EPR corresponded to the relative vascularity at the site of the fusinite both histologically and by MRI studies of vascularity using Gd-DTPA as a contrast agent. We conclude that by using the effects of fusinite on magnetic susceptibility, it can be located accurately and noninvasively with MRI and thereby the value of the use of fusinite to measure concentration of oxygen in vivo is enhanced.
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PMID:Oxygen tension in a murine tumor: a combined EPR and MRI study. 825 56

In this study, we report the synthesis and the evaluation as MRI contrast agent of arabinogalactan/pyrrolidinoxyl radicals (PCA) covalent adduct (SLAG:Spin Labelled ArabinoGalactan). Arabinogalactan was used as targeting device, as it is recognized by the asialoglycoprotein receptor specific to the hepatocytes. The higher relaxivity R1 in water of SLAG, compared with small hydrophilic nitroxyl radicals, was explained by the molecular dynamics study using EPR spectroscopy that showed some immobilization of the radical into the polysaccharide. A binding study on isolated hepatocytes revealed that SLAG still recognizes the asialoglycoprotein receptor. MR imaging was performed using spin-echo T1 weighted images on mice to compare the contrast effect obtained with SLAG and PCA after IV injection (1 mmol/kg free radical). The percent signal enhancement observed in the liver 5 min after IV injection was 40 +/- 3% and 13 +/- 5% for SLAG and PCA, respectively. The signal was also dramatically increased in the renal cortex. This latter effect as well as the prolonged duration of the contrast (+/- 3 h), indicates at least a partial nonselective biodistribution; the high concentration needed to obtain a contrast effect could account for the saturation of the asialoglycoprotein receptor and hence for the apparent nonselective biodistribution.
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PMID:Spin labelled arabinogalactan as MRI contrast agent. 829 9

Interactions of two MRI gadolinium contrast agents, gadolinium ethoxybenzyl-diethylenetriaminepentaacetate (Gd-EOB-DTPA) and gadolinium N-pentyl-1,4,7,10-tetraazacyclododecane-N',N",N'"- triacetic acid (Gd-DOTA-P), with multibilayer phospholipid dispersions prepared from 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) have been investigated with high resolution EPR spectroscopy at 95 GHz. At a resonance field of 3.3 T, EPR spectra of a small nitroxide probe, 2,2,6,6-tetramethyl-1-piperidinyloxyl (Tempo), partitioned between aqueous and membrane phases are clearly resolved, making measurements of dynamics parameters of the probe accurate and unambiguous. Results show that although the presence of the more lipophilic contrast agent, Gd-DOTA-P, can be detected within the bilayer, the structural organization of the membrane remains unaffected even at physiologically high (5 mM) concentrations. The temperature of the main phase transition of the bilayer was also unaffected to within the 0.4 degree C accuracy of its determination.
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PMID:Interaction of MRI gadolinium contrast agents with phospholipid bilayers as studied by 95 GHz EPR. 919 42

The effects of the paramagnetic oxygen sensing material, lithium phthalocyanine (LiPc) and fusinite were assessed in the brain of Mongolian gerbils and the spinal columns of rats respectively, to determine if there are histologically discernible changes in the tissue surrounding the probe material. This information is essential for the evaluation of the role of EPR oximetry in the measurements of pO2 in the CNS; the technique has great potential value for such measurements because it reports on the pO2 accurately and sensitively and, after the initial placement, measurements can be made repeatedly without invasive procedures or anesthesia. Histologic assessments demonstrated the inert nature of both the fusinite and LiPc EPR probes in rodent CNS tissue over relatively long (2 month) time periods. The fusinite suspensions and LiPc crystals (size range of approximately 100-200 microns) remained well localized to the point of injection and created mild acute tissue reaction on implantation (which appeared to resolve quickly) and virtually no tissue reaction at later times. The majority of the implanted fusinite and LiPc material was present extracellularly in the brain and spinal cord. MRI provided an accurate, noninvasive assessment of probe placement and was able to investigate pathologic effects (hemorrhage, edema, necrosis) associated with the probe placement and treatment effects.
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PMID:Histological assessment of rodent CNS tissues to EPR oximetry probe material. 926 7

This paper reports the first in vivo NMR image of the distribution of NO using the "MRI spin-trapping" technique. NO was complexed with the Fe(II)-chelate spin trap, N-methyl-D-glucamine dithiocarbamate (MGD), verified as (MGD)(2)-Fe(II)-NO by EPR, and the radical distribution was "visualized" by MR images. In rats, the (MGD)(2)-Fe(II)-NO complex was concentrated in the liver displaying significantly enhanced contrast in the vascular structure such as hepatic vein and inferior vena cava. Nitric oxide synthase was verified as the source of NO in rats with septic shock by pre-administration of the competitive inhibitor N-monomethyl-L-arginine, resulting in reduced enhancement. The NO complex was more stable in vivo and a more effective MRI contrast agent than other stable nitrogen containing radicals, such as nitroxides. The MRI spin-trapping method should be a powerful tool for visualizing spatial distributions of free radicals in pathologic organs and tissues when combined with the appropriate radical complexing agent, such as (MGD)(2)-Fe(II) used in these studies. Magn Reson Med 42:235-239, 1999.
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PMID:In vivo imaging of spin-trapped nitric oxide in rats with septic shock: MRI spin trapping. 1044 Sep 47

The trinuclear [Gd(3)(H(-)(3)taci)(2)(H(2)O)(6)](3+) complex has been characterized in aqueous solution as a model compound from the point of view of MRI: the parameters that affect proton relaxivity have been determined in a combined variable temperature, pressure, and multiple-field (17)O NMR, EPR, and NMRD study. The solution structure of the complex was found to be the same as in solid state: the total coordination number of the lanthanide(III) ion is 8 with two inner-sphere water molecules. EPR measurements proved a strong intramolecular dipole-dipole interaction between Gd(III) electron spins. This mechanism dominates electron spin relaxation at high magnetic fields (B > 5 T). Its proportion to the overall relaxation decreases with decreasing magnetic field and becomes a minor term at fields used in MRI. Consequently, it cannot increase the electronic relaxation rates to such an extent that they limit proton relaxivity. [Gd(3)(H(-)(3)taci)(2)(H(2)O)(6)](3+) undergoes a relatively slow water exchange (k(ex)(298) = (1.1 +/- 0.2) x 10(7) s(-1)) compared to the Gd(III) aqua ion, while the mechanism is much more associatively activated as shown by the activation volume (DeltaV () = (-12.7 +/- 1.5) cm(3) mol(-)(1)). The lower exchange rate, as compared to [Gd(H(2)O)(8)](3+) and [Gd(PDTA)(H(2)O)(2)](-), can be explained with the higher rigidity of the [Gd(3)(H(-)(3)taci)(2)(H(2)O)(6)](3+) which considerably slows down the transition from the eight-coordinate reactant to the nine-coordinate transition state. The unexpectedly low rotational correlation time of the complex is interpreted in terms of a spherical structure with a large hydrophobic surface avoiding the formation of a substantial hydration sphere around [Gd(3)(H(-)(3)taci)(2)(H(2)O)(6)](3+).
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PMID:Structure and Dynamics of a Trinuclear Gadolinium(III) Complex: The Effect of Intramolecular Electron Spin Relaxation on Its Proton Relaxivity(1). 1167 May 30

Proton electron double resonance imaging (PEDRI) uses the Overhauser effect to image the distribution of free-radicals in biological samples and animals. Standard MRI hardware and software is used, with the addition of hardware to irradiate the free-radical-of-interest's EPR resonance. For in vivo applications it must be implemented at a sufficiently low magnetic field to result in an EPR irradiation frequency that will penetrate the sample but will not cause excessive nonresonant power deposition therein. Many clinical MRI systems use resistive magnets that are capable of operating at 10-20 mT, and which could thus be used as PEDRI imagers with the addition of a small amount of extra hardware. This article describes the conversion of a 0.38 T whole-body MRI system for operation as a 20.1 mT small-animal PEDRI imager. The magnet power supply control electronics required a small modification to operate at the lower field strength, but no permanent hardware changes to the MRI console were necessary, and no software modification was required. Frequency down- and up-conversion was used on the NMR RF system, together with a new NMR/EPR dual-resonance RF coil assembly. The system was tested on phantoms containing free-radical solution, and was also used to image the distribution of a free-radical contrast agent injected intravenously into anesthetized mice.
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PMID:Development of a PEDRI free-radical imager using a 0.38 T clinical MRI system. 1175 57

An efficient noninvasive method for in vivo imaging of tumor oxygenation by using a low-field magnetic resonance scanner and a paramagnetic contrast agent is described. The methodology is based on Overhauser enhanced magnetic resonance imaging (OMRI), a functional imaging technique. OMRI experiments were performed on tumor-bearing mice (squamous cell carcinoma) by i.v. administration of the contrast agent Oxo63 (a highly derivatized triarylmethyl radical) at nontoxic doses in the range of 2-7 mmol/kg either as a bolus or as a continuous infusion. Spatially resolved pO(2) (oxygen concentration) images from OMRI experiments of tumor-bearing mice exhibited heterogeneous oxygenation profiles and revealed regions of hypoxia in tumors (<10 mmHg; 1 mmHg = 133 Pa). Oxygenation of tumors was enhanced on carbogen (95% O(2)/5% CO(2)) inhalation. The pO(2) measurements from OMRI were found to be in agreement with those obtained by independent polarographic measurements using a pO(2) Eppendorf electrode. This work illustrates that anatomically coregistered pO(2) maps of tumors can be readily obtained by combining the good anatomical resolution of water proton-based MRI, and the superior pO(2) sensitivity of EPR. OMRI affords the opportunity to perform noninvasive and repeated pO(2) measurements of the same animal with useful spatial (approximately 1 mm) and temporal (2 min) resolution, making this method a powerful imaging modality for small animal research to understand tumor physiology and potentially for human applications.
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PMID:Overhauser enhanced magnetic resonance imaging for tumor oximetry: coregistration of tumor anatomy and tissue oxygen concentration. 1185 18

While electron paramagnetic resonance imaging (EPRI) enables spatial mapping of free radicals in the whole body of small animals, it solely visualizes the free-radical distribution and does not typically provide anatomic visualization of the body. However, anatomic registration is often required for meaningful interpretation of the EPRI-derived free-radical images. An approach is reported for whole-body, EPRI-based, free-radical imaging along with proton MRI in mice. EPRI instrumentation with a 750-MHz narrow band microwave bridge and transverse oriented electric field reentrant resonator, with automatic coupling control and automatic tuning control capability, was used to map the spatial distribution of nitroxide free radicals in phantoms and in living mice, while low-field proton MRI at 16 MHz was used to define the anatomic structure to register the EPR images. Small capillary tubes containing an aqueous radical label were used as markers to enable image superimposition. With this coregistration technique, the EPRI free-radical images were precisely registered, enabling assignment of the location of the observed free-radical distribution within the organs of the mice. This technique enabled differentiation of the distribution and metabolism of nitroxide radicals within the major organs and body sites of living mice.
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PMID:EPR/NMR co-imaging for anatomic registration of free-radical images. 1187 Aug 45


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