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Query: UNIPROT:Q9BWK5 (MRI)
 85,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biodegradable PEGylated Gd-DTPA l-cystine copolymers, PEG-g-poly(GdDTPA-co-l-cystine), were prepared and tested as a blood pool contrast agent in mice. The biodegradable macromolecular agent was designed to be broken down into smaller Gd complexes by endogenous thiols via the disulfide-thiol exchange reaction to facilitate the clearance of Gd complexes after the contrast-enhanced MRI examination. Gd-DTPA l-cystine copolymers were synthesized by condensation polymerization of l-cystine and DTPA-dianhydride in water followed by chelating with Gd(OAc)(3). MPEG-NH(2) (MW = 2000) was then conjugated to the polymeric backbone in different ratios. The macromolecular contrast agent was readily degraded with the incubation of l-cysteine. It also demonstrated superior contrast enhancement in the heart and blood vessels as compared to a low molecular weight control agent, Gd-(DTPA-BMA). At 1 h postcontrast, the PEGylated macromolecular agent still showed prominent enhancement, while little contrast enhancement was detectable in the blood pool by the control agent. PEG-g-poly(GdDTPA-co-l-cystine) shows promise as an MR blood pool imaging agent.
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PMID:PEG-g-poly(GdDTPA-co-L-cystine): a biodegradable macromolecular blood pool contrast agent for MR imaging. 1554 11

We evaluated the transport of Gadolinium-diethylenetriaminepentaacetate-bismethylamide (Gd-DTPA-BMA) through the round window (RW) membrane into the perilymphatic space with 4.7-T MRI in an animal study and 1.5-T MRI in humans. After administration of Gd-DTPA-BMA onto the intact RW membrane of guinea pig, Gd-DTPA-BMA uptake was observed in the basal turn and part of the second turn within 40 min. The scala tympani, scala vestibuli, the fibrous part of the spiral ligament and semicircular canal all showed uptake of Gd-DTPA-BMA. All turns of the cochlea were filled with Gd within 10 min in the perforated RW membrane administration group and within 30 min in the intravenous administration group. In patients who accepted middle ear injection of Gd-DTPA-BMA, uptake was observed within 2 h in the basal turn and semicircular canal. After 12 h the apex did still not show any uptake. Gd-DTPA-BMA is transported from the RW to the semicircular canal, the scala tympani and scala vestibuli without passing the helicotrema.
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PMID:Communication between the perilymphatic scalae and spiral ligament visualized by in vivo MRI. 1572 85

The structures of polydisulfide-based biodegradable macromolecular Gd(III) complexes were modified to improve their in vivo retention time and MRI contrast enhancement. Steric hindrance was introduced around the disulfide bonds to control their access to free thiols in order to alter the degradation rate of the copolymers. Two new macromolecular agents, (Gd-DTPA)-cystine copolymers (GDCP) and (Gd-DTPA)-cystine diethyl ester copolymers (GDCEP), were prepared. Both agents were readily degraded in vitro and in vivo by the disulfide-thiol exchange reaction, but at a slow rate. The introduction of COOH and COOEt groups slowed down the degradation of the copolymers in the incubation with 15 microM cysteine. Metabolic degradation products were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry in the urine samples from rats injected with the agents. The T(1) relaxivity (r(1)) was 5.43 mM(-1)s(-1) for GDCP, and 5.86 mM(-1)s(-1) for GDCEP, respectively, at 3T. MRI contrast enhancement of both agents was studied in nude mice bearing MDA-BM-231 human breast carcinoma xenografts, on a Siemens Trio 3T scanner. The modified agents resulted in more significant contrast enhancement in the blood pool and tumor periphery than (Gd-DTPA)-cystamine copolymers (GDCC) and a low-molecular-weight control agent, Gd-(DTPA-BMA), at a dose of 0.1 mmol-Gd/kg. The results demonstrate that the structural modification of the biodegradable macromolecular Gd(III) complexes resulted in a relatively slow degradation of the macromolecules and significantly improved in vivo contrast enhancement. The modified agents show promise for use in investigations of blood pool and cancer by contrast-enhanced (CE) MRI.
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PMID:Contrast-enhanced MRI with new biodegradable macromolecular Gd(III) complexes in tumor-bearing mice. 1579 38

The potential neurotoxic effects of gadolinium (Gd)-based compounds for enhanced MRI are not completely understood. We investigated electroencephalography changes induced by ionic and non-ionic Gd-based compounds administered intravenously in patients affected by lesions of the central nervous system (CNS) characterized by breakdown of the blood-brain barrier. This double-blind, randomized, study of two parallel groups involved 40 patients scheduled for an MRI examination with contrast medium for known CNS lesions. Twenty patients were randomly allocated to receive non-ionic Gd-DTPA-BMA/gadodiamide and 20 patients were randomly allocated to receive ionic Gd-DTPA/gadopentetate. For both groups the intravenous dose was 0.1 mmol/kg body weight. Three electroencephalography recordings were performed: immediately before, during, and 15 min after contrast medium injection. Mean and peak frequencies of the beta band and absolute power of the delta and/or theta bands of the electroencephalograms (EEGs) were noted. Each EEG was also evaluated to detect any alterations. The values of the 8-12 Hz band showed a significant increase during and after injection versus baseline in the gadopentetate group (P<0.05) and a significant decrease during injection in the gadodiamide group (P<0.05). The values of the 12-16 Hz band showed a significant increase versus baseline during and after injection in the gadopentetate group (P<0.05). The electrophysiological method based on computerised spectral analysis is a sensitive tool for evaluating effects of contrast media on brain bio-electric activity. EEG changes are detectable, even in the absence of any clinical evidence. It would appear that there might be clinical advantages in the use of non-ionic compounds.
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PMID:Effects of ionic and non-ionic paramagnetic contrast media on brain bio-electric activity. 1613 84

Tumour angiogenesis is a tightly regulated process involving cross-talk between tumour cells and the host tissue. The underlying mechanisms that regulate such interactions remain largely unknown. NG2 is a transmembrane proteoglycan whose presence on transformed cells has been demonstrated to increase proliferation in vitro and angiogenesis in vivo. To study the effects of NG2 during tumour growth and progression, we engineered an NG2 positive human glioma cell line (U251-NG2) from parental NG2 negative cells (U251-WT) and implanted both cell types stereotactically into immunodeficient nude rat brains. The tumours were longitudinally monitored in vivo using multispectral MRI employing two differently sized contrast agents (Gd-DTPA-BMA and Gadomer) to assess vascular leakiness, vasogenic oedema, tumour volumes and necrosis. Comparisons of Gd-DTPA-BMA and Gadomer revealed differences in their spatial distribution in the U251-NG2 and U251-WT tumours. The U251-NG2 tumours exhibited a higher leakiness of the larger molecular weight Gadomer and displayed a stronger vasogenic oedema (69.9 +/- 15.2, P = 0.018, compared to the controls (10.7 +/- 7.7). Moreover, immunohistochemistry and electron microscopy revealed that the U251-NG2 tumours had a higher microvascular density (11.81 +/- 0.54; P = 0.0010) compared to controls (5.76 +/- 0.87), with vessels that displayed larger gaps between the endothelial cells. Thus, tumour cells can regulate both the function and structure of the host-derived tumour vasculature through NG2 expression, suggesting a role for NG2 in the cross-talk between tumour-host compartments.
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PMID:NG2 expression regulates vascular morphology and function in human brain tumours. 1625 23

The OH radical scavenging activity of a series of Gd(III) MRI contrast media, such as Gd(III)DTPA, Gd(III)BMA and Gd(III)DO3A, were evaluated by means of EPR spin trapping measurements. The second order reaction rate constant (k2) occurring between Gd(III)DTPA and OH radical was estimated to be 3.26 x 10(10) (M(-1)s(-1)), which was ten times larger than that of the free ligand DTPA (3.86 x 10(9) M(-1)s(-1). The k2 values of Gd(III)BMA and Gd(III)DO3A were also determined to be 1.31 x 10(10) and 1.77 x 10(10) (M(-1)s(1)), respectively. The present results suggest that widely used Gd(III) containing MRI reagent exhibit OH radical scavenging activity, and these values of k2 are same order as that of ascorbic acid (1.16 x 10(10) M(-1)s(-1)) which has been well established to be the most powerful OH radical scavenger. Based on the EPR measurements performed for these Gd(III) complexes, a possible reaction mechanism of the OH radical scavenging action of these MRI contrast media will be discussed.
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PMID:Flow-injection EPR investigation on OH radical scavenging activity of Gd(III) containing MRI contrast media. 1808 64

The efficacy of polydisulfide-based biodegradable macromolecular contrast agents for characterizing tumor angiogenesis was investigated in a mouse model using dynamic contrast-enhanced MRI (DCE-MRI). Biodegradable macromolecular MRI contrast agents, gadopentetate dimeglumine (Gd-DTPA) cystamine copolymers (GDCC), and Gd-DTPA cystine copolymers (GDCP), with molecular weights of 20 and 70 kDa were used in the study. Gadodiamide (Gd [DTPA-BMA]) and albumin labeled with Gd-DTPA [albumin-(Gd-DTPA)] were used as the controls. The DCE-MRI studies were performed in nude mice bearing prostate tumor xenografts from the MDA-PCa-2b cell line. Tumor angiogenic kinetic parameters, including endothelial transfer coefficient (K(PS)), fractional tumor plasma volume (f(PV)), and permeability surface area product (PS), were estimated from the DCE-MRI data using a two-compartment model. The K(PS) and f(PV) values estimated by the biodegradable macromolecular contrast agents were between those estimated by Gd(DTPA-BMA) and albumin-(Gd-DTPA). The parameters estimated by the agent with a slow degradation rate and high molecular weight, GDCP-70 (K(PS) = 2.09 +/- 0.50 ml/min/100 cc and f(PV) = 0.075 +/- 0.021), were closer to those by albumin-(Gd-DTPA) (K(PS) = 1.43 +/- 0.64 ml/min/100 cc and f(PV) = 0.044 +/- 0.007) than by other agents with relatively low molecular weight or rapid degradation rate. The polydisulfide-based biodegradable macromolecular contrast agents are promising for characterizing tumor vascularity and angiogenesis with DCE-MRI.
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PMID:Characterization of tumor angiogenesis with dynamic contrast-enhanced MRI and biodegradable macromolecular contrast agents in mice. 1902 2

To monitor the release of cargo molecules from nanocarriers, a novel MRI/MRS technique was developed and tested. This novel approach uses a simultaneous encapsulation of superparamagnetic iron oxide (SPIO) nanoparticles and either a gadolinium (Gd)-based paramagnetic contrast agent, Gd-diethylenetriamine pentaacetic acid bismethylamide(GdDTPA-BMA), for MRI, or an anticancer agent, 5-fluorouracil (5-FU), for MRS. These agents have significantly different diffusion properties due to their different molecular sizes. Strong negative signal enhancement due to the T(2) effects of SPIO dominates the positive T(1) contrast generated by GdDTPA-BMA when SPIO and GdDTPA-BMA are in close proximity (intact form). Positive T(1) contrast becomes evident upon release of GdDTPA-BMA from the carrier once the distance between GdDTPA-BMA and SPIO molecules is beyond the T(2) enhancement range. Similarly, intact nanocarriers loaded with 5-FU and SPIO have a broad (19)F resonance line because line-width is inversely proportional to T*2, while free 5-FU appears as a narrow resonance line once it is released from the liposomes. This technique allowed monitoring of the release of cargo molecules from liposomes encapsulating both SPIO and either GdDTPA-BMA or 5-FU by MRI/MRS in vitro using 2% agarose gel phantoms. Experimental results demonstrate successful demarcation of the released cargo molecules vs. encapsulated molecules.
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PMID:Monitoring of release of cargo from nanocarriers by MRI/MR spectroscopy (MRS): significance of T2/T2* effect of iron particles. 1925 73

Imaging techniques are under development to facilitate early analysis of spatial patterns of tumor response to combined radiation and antivascular gene therapy. A genetically modified, replication defective adenoviral vector (Ad.EGR-TNFalpha), injected intratumorally, mediates infected cells to express tumor necrosis factor alpha (TNFalpha), which is increased after exposure to radiation. The goal of this study was to characterize an image based "signature" for response to this combined radiation and gene therapy in mice with human prostate xenografts. This study is part of an imaged guided therapy project where such a signature would be useful in guiding subsequent treatments. Changes in the tumor micro-environment were assessed using MRI registered with electron paramagnetic resonance imaging which provides images of tissue oxygenation. Dynamic contrast-enhanced MRI was used to assess tissue perfusion. When compared with null vector (control) treatment, the ratio of contrast agent (Gd-DTPA-BMA) washout rate to uptake rate was lower (P = 0.001) after treatment, suggesting a more balanced perfusion. Concomitantly, oxygenation significantly increased in the treated animals and decreased or did not change in the control animals (P < 0.025). This is the first report of minimally invasive, quantitative, absolute oxygen measurements correlated with tissue perfusion in vivo.
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PMID:Characterization of response to radiation mediated gene therapy by means of multimodality imaging. 1944 82

The exine coatings of spores can be used to encapsulate drug molecules. We have demonstrated that these microcapsules can be filled with a commercial gadolinium(III) MRI contrast agent (in this proof of concept study Gd-DTPA-BMA was used) which is slowly released in plasma due to enzymatic digestion of the capsule.
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PMID:MRI contrast agent delivery using spore capsules: controlled release in blood plasma. 1984 3


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