• Bulletin of the Korean Chemical Society
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• v.30 no.4
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• pp.849-852
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• 2009

The work describes EPR and 17O NMR measurements followed by theoretical calculation of the rotational correlation time $({\tau}_R)$, the water residence time $({\tau}_m)$, and the longitudinal electronic spin relaxation time $(T_{le})$(T_1e) for two new gadolinium complexes 1 and 2 of the type [$Gd(L)(H_2O)$] (L = tranexamic esters) in order to investigate their efficiency as a paramagnetic contrast agent (PCA). Of three correlation times, τR plays a major and predominant role to the unusually high relaxivity of 1 and 2 as compared with that of clinically approved MR CAs such as [$Gd(DTPA)(H_2O)]2‐ (Magnevist${\circledR}$), [Gd(DTPA-BMA)(H2O)] (Omniscan${\circledR}$), and $[Gd(DOTA)(H_2O)]^-$ (Dotarem${\circledR}$). The presence of bulky tranexamic ester in the ligand seems to be responsible for the conformational rigidity, which in turn causes such great an increase in ${\tau}_R$.

• Bulletin of the Korean Chemical Society
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• v.34 no.10
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• pp.2900-2904
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• 2013

We present the synthesis and characterization of DTPA-bis(histidylamide) (1a), DTPA-bis(aspartamide) (1b), and their gadolinium complexes of the type $[Gd(L)(H_2O)]$ (2a:L = 1a; 2b:L = 1b). Thermodynamic stabilities and $R_1$ relaxivities of 2a-b compare well with Omniscan$^{(R)}$, a well-known commercial, extracellular (ECF) MRI CA which adopts the DTPA-bis(amide) framework for the chelate: $R_1$ = 5.5 and 5.1 $mM^{-1}$ for 2a and 2b, respectively. Addition of the Cu(II) ion to a solution containing 2b triggers relaxivity enhancement to raise $R_1$ as high as 15.3 $mM^{-1}$, which corresponds to a 300% enhancement. Such an increase levels off at the concentration beyond two equiv. of Cu(II), suggesting the formation of a trimetallic ($Gd/Cu_2$) complex in situ. Such a relaxivity increase is almost negligible with Zn(II) and other endogenous ions such as Na(I), K(I), Mg(II), and Ca(II). In vivo MR images and the signal-to-noise ratio (SNR) obtained with an aqueous mixture of 2b and Cu(II) ion in an 1:2 ratio demonstrate the potentiality of 2 as a copper responsive MRI CA.

• Investigative Magnetic Resonance Imaging
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• v.15 no.2
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• pp.139-145
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• 2011

Purpose : To assess the frequency and severity of acute adverse reactions to intravenous administration of gadolinium-based contrast agents using computerized reporting system at a single large academic institution. Materials and Methods : We assessed data from electronic hospital information system from October 2008 to December 2010. Reactions were classified as mild, moderate, or severe. We compared the frequency of adverse reactions among three contrast agents (Gd-BT-DO3A, Gd-DTPA and Gd-EOB-DTPA). Results : The total number of administrated contrast agents was 33,600, and the number of administration of Gd-BT-DO3A, Gd-DTPA and Gd-EOB-DTPA were 20,824 (62%), 10,417 (31%) and 2,359 (7%), respectively. Total 39 adverse reactions were reported accounting for 0.1161% of all administrations. The incidences of adverse reactions were 0.1248% (26/39, 67%) for Gd-BT-DO3A, 0.0768% (8/39, 21%) for Gd-DTPA, and 0.2120% (5/39, 13%) for Gd-EOB-DTPA. The difference of frequencies of adverse reaction among three contrast agents was not significant. Most cases of the adverse effect were mild (35/39, 89.7%). Moderate and severe adverse reactions were encountered in two patients, respectively. Conclusion : Among Koreans, adverse effects were rare, and especially, moderate to severe adverse reactions were much rarer. There was no difference among the frequencies of adverse reactions caused by three different contrast agents.

• The Journal of the Korea Contents Association
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• v.8 no.11
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• pp.210-216
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• 2008

In this study, image comparisons were carried out using a MRI contrast medium which was derived by mixing a polyaminocarboxylic ligand and a gadolinium (III) transition metal which is paramagnetic and has good neutron absorbing capabilities with Gd-DTPA which is currently being used widely in the clinical setting. By using a 1.0T (Harmony, SIEMENS) MR equipment, phantoms of which 100cc of saline was diluted with a diethylenetriaminetriacetic acid derivative and Gd-DTPA were imaged. The amount of diethylenetriaminetriacetic acid and Gd-DTPA which was diluted into the 100cc of saline was 0.05mmol/L, 0.1mmol/L, 0.15mmol/L, 0.2mmol/L, 0.3mmol/L, 0.5mmol/L, 1.0mmol/L, 2.0mmol/L, 3.0mmol/L and 4.9mmol/L respectively. Head coils were used and while fixing the SE pulse sequence and image variable (as TE is 14ms, 1NEX with a 256x201 matrix), the signal intensity and simple contrast ratios according to changing concentrations and TR were compared with various TR at 300ms, 400ms, 500ms, 600ms, 700ms, 800ms, 900ms, 1000ms, 1200ms, 1400ms and 1600ms. According to the comparison results of the signal intensity of the image based on changes in contrast medium concentrations and TR, the differences in signal intensity between the two contrast mediums were found to be small at $1.0{\sim}2.0mmol/L$ when the highest signal intensity was achieved. However, at concentrations of 1.0mmol/L or less, the signal intensity was markedly higher in the Diethylenetriaminetriacetic acid derivative than in the Gd-DTPA complex. It was also found that the differences in the signal intensities demonstrated by the concentrations of the contrast mediums were affected by the TR. Accordingly, the efficacy of the Diethylenetriaminetriacetic acid derivative was shown to be better than the Gd-DTPA and also possible to get the optimum image quality by the use of an appropriate TR with appropriate concentrations of contrast medium.

• Radiation Oncology Journal
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• v.34 no.1
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• pp.64-75
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• 2016

Purpose: In order to evaluate the relationship between the dose to the liver parenchyma and focal liver reaction (FLR) after stereotactic ablative body radiotherapy (SABR), we suggest a novel method using a three-dimensional dose distribution and change in signal intensity of gadoxetate disodium-gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) hepatobiliary phase images. Materials and Methods: In our method, change of the signal intensity between the pretreatment and follow-up hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI was calculated and then threshold dose (TD) for developing FLR was obtained from correlation of dose with the change of the signal intensity. For validation of the method, TDs for six patients, who had been treated for liver cancer with SABR with 45-60 Gy in 3 fractions, were calculated using the method, and we evaluated concordance between volume enclosed by isodose of TD by the method and volume identified as FLR by a physician. Results: The dose to normal liver was correlated with change in signal intensity between pretreatment and follow-up MRI with a median $R^2$ of 0.935 (range, 0.748 to 0.985). The median TD by the method was 23.5 Gy (range, 18.3 to 39.4 Gy). The median value of concordance was 84.5% (range, 44.7% to 95.9%). Conclusion: Our method is capable of providing a quantitative evaluation of the relationship between dose and intensity changes on follow-up MRI, as well as determining individual TD for developing FLR. We expect our method to provide better information about the individual relationship between dose and FLR in radiotherapy for liver cancer.

• The Journal of the Korea Contents Association
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• v.17 no.7
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• pp.215-221
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• 2017

The purpose of present study was to assess whether Gd-EOB-DTPA with gadolinium-based contrast agent administration affects fat quantification using the two-point Dixon technique. Between April 2016 and September, 60 patients who underwent hepatic fat quantification using the two-point Dixon technique were divided into two group (normal liver donors=30, abnormal hepatic steatosis=30) and we compared the variability of mean fat fraction before and after administration Gd-EOB-DTPA. As a results, in both group, fat fraction after injection Gd-EOB-DTPA was significantly decreased (normal liver donors -33.8%, hepatic steatosis -47.2%) compared to before injection Gd-EOB-DTPA, suggesting that Gd-EOB-DTPA affects fat quatification using two-point Dixon technique. In conclusion, hepatic fat quantification using the two-point Dixon technique could maintain diagnostic value by acquiring images before administration Gd-EOB-DTPA.

• Investigative Magnetic Resonance Imaging
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• v.6 no.2
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• pp.158-165
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• 2002

Purpose : To evaluate the effect of Gd-DTPA on signal intensity of diffusion-weighted magnetic resonance(MR) image and apparent diffuse coefficient (ADC) in dog brain with hype racute stroke. Materials and methods : Experimental canine model of hyperacute cerebral infarction was made by selective intraarterial embolization with particulate embolic material. Diffusion-weighted MR imaging was performed in five dogs at 1 hour after the embolization of internal carotid artery. After intravenous bolus injection of Gd- DTPA, additional 11 diffusion-weighted MR images were serially obtained from 2 minutes to 90 minutes after injection in each dog. The author evaluated findings of hyperacute cerebral infarction on diffusion-weighted MR imaging, and calculated mean signal intensity and mean ADC in infarcted region and contralateral normal region. Statistical analysis of mean signal intensity, mean ADC and contrast-noise ratio before and after Gd-DTPA injection was performed. Results : Hyperacute cerebral infarction developed in all five dogs on diffusion-weighted MR images obtained 1 hour after embolization. The area of hyperacute infarction had steady increase in signal intensity on diffusion-weighted MR image and decrease in ADC. In normal perfusion area, decrease in signal intensity was observed at 2 minutes the Gd-DTPA injection, whereas ADC did not changed. Conclusion : Intravenous injection of Gd-DTPA had no influence on ADC in both hyperacute infarction and normally perfused are a, but caused initial transient signal reduction in normally perfused area on diffusion-weighted MR image due to susceptibility effect of Gd-DTPA. It is important to calculate ADC in evaluating the effect of diffusion after injection of Gd-DTPA.

• Bulletin of the Korean Chemical Society
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• v.31 no.5
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• pp.1177-1181
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• 2010

The synthesis and characterization of gold nanoparticles coated by Gd-chelate (GdL@Au) is described, where L is a conjugate of DTPA (DTPA = diethylenetriamine-N,N,N',N",N"-pentaacetic acid) and 4-aminothiophenol. These particles are obtained by the replacement of citrate from the gold nanoparticle surfaces with gadolinium chelate (GdL). The average size of GdL@Au is 12 nm with a loading of GdL reaching up to $1.4{\times}10^3$ per particles, and they demonstrate very high r1 relaxivity (${\sim}10^4mM^{-1}s^{-1}$) and the r1 relaxivity per [Gd] is as high as $10mM^{-1}s{-1}$. Here, we also describe the use of bimodality of this contrast agent (CA) as a highly efficient CT contrast agent based on gold nanoparticles (GNPs) that overcome the limitations of iodine based contrast agent. The MTT assay performed on this CAs reveals the cytotoxicity as low as that for Omniscan$^{(R)}$ in the concentration range required to obtain intensity enhancement in the in vivo MRI study.

• Investigative Magnetic Resonance Imaging
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• v.17 no.4
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• pp.259-266
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• 2013

Purpose : To investigate the blood pharmacokinetics and bio-distribution of DTPA-bis-amide (L3) Gd(III) complexes. Materials and Methods: The pharmacokinetics and bio-distribution of Gd $(L3)(H_2O){\cdot}nH_2O$ were investigated in Sprague-Dawley rats after intravenous administration at a dose of 0.1 mmol Gd/kg. The Gd content in the blood, various tissues, and organs was determined by ICP-AES. Blood pharmacokinetic parameters were calculated using a two-compartment model. Results: The half-lives of ${\alpha}$ phase and ${\beta}$ phase Gd $(L3)(H_2O){\cdot}nH_2O$ were $2.286{\pm}0.11$ min and $146.1{\pm}7.5$ min, respectively. The bio-distribution properties reveal that the complex is mainly excreted by the renal pathway, and possibly excreted by the hepatobiliary route. The concentration ratio of Gd (III) was significantly higher in the liver and spleen than in other organs, and small amounts of Gd (III) ion were detected in the blood or other tissues of rats only after 7 days of intravenous administration. Conclusion: The MRI contrast agent Gd $(L3)(H_2O){\cdot}nH_2O$ provides prolonged blood pool retention in the circulation and then clears rapidly with minimal accumulation of Gd(III) ions. The synthesis of gadolinium complexes with well-balanced lipophilicity and hydrophilicity shows promise for their further development as blood pool MRI contrast agents.

• Investigative Magnetic Resonance Imaging
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• v.8 no.2
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• pp.100-108
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• 2004

Purpose : Early degeneration of articular cartilage is accompanied by a loss of glycosaminoglycan (GAG) and the consequent change of the integrity. The purpose of this study was to biochemically quantify the loss of GAG, and to evaluate the $Gd(DTPA)^{2-}$-enhanced, and T1, T2, rho relaxation map for detection of the early degeneration of cartilage. Materials and Methods : A cartilage-bone block in size of $8mm\;\times\;10mm$ was acquired from the patella in each of three pigs. Quantitative analysis of GAG of cartilage was performed at spectrophotometry by use of dimethylmethylene blue. Each of cartilage blocks was cultured in one of three different media: two different culture media (0.2 mg/ml trypsin solution, 1mM Gd $(DTPA)^{2-}$ mixed trypsin solution) and the control media (phosphate buffered saline (PBS)). The cartilage blocks were cultured for 5 hrs, during which MR images of the blocks were obtained at one hour interval (0 hr, 1 hr, 2 hr, 3 hr, 4 hr, 5 hr). And then, additional culture was done for 24 hrs and 48 hrs. Both T1-weighted image (TR/TE, 450/22 ms), and mixed-echo sequence (TR/TE, 760/21-168ms; 8 echoes) were obtained at all times using field of view 50 mm, slice thickness 2 mm, and matrix $256\times512$. The MRI data were analyzed with pixel-by-pixel comparisons. The cultured cartilage-bone blocks were microscopically observed using hematoxylin & eosin, toluidine blue, alcian blue, and trichrome stains. Results : At quantitation analysis, GAG concentration in the culture solutions was proportional to the culture durations. The T1-signal of the cartilage-bone block cultured in the $Gd(DTPA)^{2-}$ mixed solution was significantly higher ($42\%$ in average, p<0.05) than that of the cartilage-bone block cultured in the trypsin solution alone. The T1, T2, rho relaxation times of cultured tissue were not significantly correlated with culture duration (p>0.05). However the focal increase in T1 relaxation time at superficial and transitional layers of cartilage was seen in $Gd(DTPA)^{2-}$ mixed culture. Toluidine blue and alcian blue stains revealed multiple defects in whole thickness of the cartilage cultured in trypsin media. Conclusion : The quantitative analysis showed gradual loss of GAG proportional to the culture duration. Microimagings of cartilage with $Gd(DTPA)^{2-}$-enhancement, relaxation maps were available by pixel size of $97.9\times195\;{\mu}m$. Loss of GAG over time better demonstrated with $Gd(DTPA)^{2-}$-enhanced images than with T1, T2, rho relaxation maps. Therefore $Gd(DTPA)^{2-}$-enhanced T1-weighted image is superior for detection of early degeneration of cartilage.