• Nuclear Medicine and Molecular Imaging
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• v.42 no.4
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• pp.307-313
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• 2008

Purpose: Vascular endothelial growth factor (VEGF) and its receptor, fetal liver kinase 1 (Flk-1), play an important role in vascular permeability and tumor angiogenesis. The aim of this study is to evaluate the therapeutic efficacy of $^{131}I$ labeled anti-Flk-1 monoclonal antibody (DC101) on the growth of melanoma tumor, which is known to be very aggressive in vivo. Materials and Methods: Balb/c nude mice were injected subcutaneously with melanoma cells in the right flank. Tumors were allowed to grow up to $200-250\;mm^3$ in volume. Gamma camera imaging and biodistribution studies were performed to identify an uptake of $^{131}I$-DC101 in various organs. Mice with tumor were randomly divided into five groups (10 mice per group) and injected intravenously; control PBS (group 1), $^{131}I$-DC101 $50\;{\mu}g/mouse$ (group 2), non-labeled DC101 $50\;{\mu}g/mouse$ (group 3), $^{131}I$-DC101 $30\;{\mu}g/mouse$ (group 4) and $15\;{\mu}g/mouse$ (group 5) every 3 or 4 days for 20 days. Tumor volume was measured with caliper twice a week. Results: In gamma camera images, the uptake of $^{131}I$-DC101 into tumor and thyroid was increased with time. Biodistribution results showed that the radioactivity of blood and other major organ was gradually decreased with time whereas tumor uptake was increased up to 48 hr and then decreased. After 4th injection of $^{131}I$-DC101, tumor volume of group 2 and 4 was significantly smaller than that group 1. After 5th injection, the tumor volume of group 5 also significantly reduced. Conclusion: These results indicated that delivery of $^{131}I$ to tumor using FlK-1 antibody, DC101, effectively blocks tumor growth in aggressive melanoma xenograft model.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.813-822
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• 1995

Background: Bronchial hyperresponsiveness and abnormal response such as a loss of distensibility are pathophysiologic characteristics if bronchial asthma. The only means of direct in vivo measurement of airway size had been a tantalium bronchography, until high-resolution computed tomography(HRCT) enabled to measure noninvasively two dimensional airway area more accurately and reliably. Method: To investigate airway area responses to bronchial provocation with methacholine and evaluate the major sites of bronchial constriction in patients with bronchial asthma. We examined HRCT scans in five patients with bronchial asthma who had significant bronchoconstriction(20% or more decrease in $FEV_1$) using CT scanner(5,000T CT, Shimadzu Co, Japan) before and in 3~5 min. after methacholine inhalation. Airways which were matched by parenchymal anatomic landmarks in each patient before and after methacholine inhalation were measured using film scanner(TZ-3X scanner; Truvel Co. Chatsworth CA, USA) and a semiautomated region growing method. Results: 1) We identified 9 to 12 airways in each patient which were matched by parenchymal anatomic landmarks before and after methacholine inhalation. 2) Airway responses to methacholine are quite different even in a patient. 3) The constriction of small airways(average diameter <2 mm; area < $3.14mm^2$) was 48.7%(8.3; SEM, n=43), being more prominant than that of large airways(average diameter >2 mm; area > $3.14mm^2$), 53.8% (4.4;SEM, n=10), but not significantly different(p>0.05). 4) There was no significant difference in the degree of constriction between upper(44.3% +5.8; mean + SEM, n=30) and lower lung regions(56.7% +4.5, n=23). Conclusions: Thus airway responses to methacholine bronchoprovocation is quite variable in a patient with bronchial asthma and has no typical pattern in patients with bronchial asthma.

• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1309-1315
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• 2000

Objectives : We performed an in vivo experiment to investigate the effect of $^{166}Holmium$ and $^{166}Holmium$-chitosan complex($^{166}Ho$-CHICO) on the normal brain of rats and to determine the sublethal dose of $^{166}Ho$-CHICO. Materials and Methods : $^{166}Ho$ is a beta and gamma ray emitter. $^{166}Ho$-CHICO is a novel radio-pharmaceutical complex with chitosan to facilitate the transport of $^{166}Ho$ obtained from Korea Atomic Energy Research Center(Taejon, Korea). It is in acidic form and becomes gel state at alkaline pH. One hundred and seventy consecutive rats were divided into four groups : $^{166}Ho$ treated(n＝50), $^{166}Ho$-CHICO treated(n＝57), saline treated(n＝5) and chitosan treated(n＝5) groups. $^{166}Ho$ and $^{166}Ho$-CHICO were injected into the rat brain stereotactically with various doses of 0.1mCi/$20{\mu}l$, 0.2mCi/$20{\mu}l$, 0.3mCi/$20{\mu}l$, and 0.4mCi/$20{\mu}l$ using an automated microinjector. Nuclear imaging, histopathological and hematological studies were performed in 10 rats in each group at 1 day, 3days, 7 days, 1 month and 3 months after the injections. Results : An infiltration of inflammatory cells and necrotic changes were noted in $^{166}Ho$ treated group at 1 week after the injection. A wedge-shaped tissue defect due to necrosis, lined with infiltrated glial cells in $^{166}Ho$ treated group and a cystic defect lined with reactive astroglial cells in $^{166}Holmium$-CHICO treated group at 3 months after the injection were observed. $^{166}Ho$ alone without chitosan leaked out and caused necrotic lesion on the cerebral surface but $^{166}Holmium$-CHICO treated group did not show this feature. As the dose of $^{166}Ho$ increased, the mortality rates were also increased. The mortality rate of the $^{166}Holmium$-CHICO group was higher than the $^{166}Ho$ treated group at a dose of 0.4mCi/$20{\mu}l$/300g. There was no detectable radioactivity due to the leakage or extravasation from the injected site of the brain on the scintigraphy performed at 1 hour, 24 hours and 48 hours after the injection. There was also no detectable activity of $^{166}Holmium$-CHICO in other organs including spleen, liver and kidney. Conclusions : $^{166}Ho$-CHICO did not leak out to the critical cortical surface of the brain from the injection site and induced radiation changes of the parenchyma around the injection site without cortical damage. The sublethal dose of $^{166}Ho$-CHICO for the normal brain in rats was determined to be 0.2mCi/$20{\mu}l$/300g.

• Investigative Magnetic Resonance Imaging
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• v.18 no.4
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• pp.303-313
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• 2014

Purpose : In-vivo conductivity reconstruction using transmit field ($B_1{^+}$) information of MRI was proposed. We assessed the accuracy of conductivity reconstruction in the presence of statistical noise in complex $B_1{^+}$ map and provided a parametric model of the conductivity-to-noise ratio value. Materials and Methods: The $B_1{^+}$ distribution was simulated for a cylindrical phantom model. By adding complex Gaussian noise to the simulated $B_1{^+}$ map, quantitative conductivity estimation error was evaluated. The quantitative evaluation process was repeated over several different parameters such as Larmor frequency, object radius and SNR of $B_1{^+}$ map. A parametric model for the conductivity-to-noise ratio was developed according to these various parameters. Results: According to the simulation results, conductivity estimation is more sensitive to statistical noise in $B_1{^+}$ phase than to noise in $B_1{^+}$ magnitude. The conductivity estimate of the object of interest does not depend on the external object surrounding it. The conductivity-to-noise ratio is proportional to the signal-to-noise ratio of the $B_1{^+}$ map, Larmor frequency, the conductivity value itself and the number of averaged pixels. To estimate accurate conductivity value of the targeted tissue, SNR of $B_1{^+}$ map and adequate filtering size have to be taken into account for conductivity reconstruction process. In addition, the simulation result was verified at 3T conventional MRI scanner. Conclusion: Through all these relationships, quantitative conductivity estimation error due to statistical noise in $B_1{^+}$ map is modeled. By using this model, further issues regarding filtering and reconstruction algorithms can be investigated for MREPT.

• The Korean Journal of Nuclear Medicine
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• v.35 no.1
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• pp.69-74
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• 2001

Purpose: $^{99m}Tc$-HMPAO is a radiopharmaceutical for imaging cerebral blood flow. HMPAO (RR, SS)-4.8-diaza-3,6,6,9-tetramethylundecan-2,10- dione bisoxime) has three stereoismers such as, meso-. d-, and l-HMPAO. Techentium complexes of meso-HMPAO and d,l-HMPAO are known to have different in vivo brain uptakes. In this study, enantiomers of HMPAO (d-HMPAO and l-HMPAO) were separated from d,l-HMPAO. These enantiomers were labeled with $^{99m}Tc$ and the biodistribution studies were performed in mice. Materials and Methods: An intermediate imine product was produced from 2,3-butanedione monooxime and 2,2-dimethyl-1,3-propanediamine (54% yield) and was reduced into a mixture of three isomers (35% yield). The meso-isomer was separated from d,l-mixture by repeated fractional crystallization (11 % yield). The d- and l-enantiomers were subsequently separated by co-crystallization with optical isomers of tartaric acid (25% and 5% yield. respectively). Each enantiomeric HMPAO was labeled with $^{99m}Tc$ by reacting with $SnCI_2{\cdot}2H_2O\;and\;^{99m}Tc$-pertechnetate. Biodistribution study was performed 1 hr after tail vein injection to ICR mice. Results: Radiochemical purities of each compound were over 80%. In biodistribution study. the brain uptakes of d,l- d- and l-form were 1.34, 1.12 and 1.67% ID/g, respectively. In case of l-lsomer the brain uptake was higher (1.5 fold) than d-isomer. Conclusion: We successfully purified each enantiomeric HMPAO. In biodistribution study of stereoismers of $^{99m}Tc$-HMPAO in mice, l-HMPAO may show better brain image than d,l-HMPAO which was supplied in a commercial kit.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.1
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• pp.72-78
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• 2009

Purpose: Bone mineral density (BMD) measurements need to be precise enough to be capable of detecting small changes in bone mass of rats. Using a regular dual-energy X-ray absorptiometry (DXA), we measured many BMD of various skeletal sites in rats to examine precision of DXA in relation to the repositioning on the bones of rats. Materials and Methods: Using DXA and small animal software, scans were performed 4 times in all 12 male rats without repositioning (Group 1a). Another four scans for 6 of 12 rats were done with repositioning between scans (Group 2). Customized regions of interest (ROIs), encapsulate the right hind limb, L1-4, skull and pelvic bones were drawn at each measurement. The precision of the measurements was evaluated by measuring the coefficient of variation (CV) of four measurements of BMD at each skeletal site of all rats with or without repositioning. Significance of differences between group 1b (six rats out of group 1a, which were come under group 2) and group2 were evaluated with Wilcoxon Signed Rank Sum Test. Results: CVs obtained at different skeletal sites of all measurements in Group 1b and 2. It was $3.51{\pm}1.20$, $ 2.62{\pm}1.20$ for the hindlimb (p=0.173), $3.83{\pm}2.02$, $4.59{\pm}2.02$ for L1-4 (p=0.600), $3.73{\pm}1.87$, $1.53{\pm}0.89$ for skull (p=0.046), and $2.92{\pm}0.60$, $1.45{\pm}0.60$ for pelvic bones (p=0.075). Conclusion: Our study demonstrates that the DXA technique has the precision necessary when used to assess BMD for various skeletal sites in rats regardless of repositioning.

• Journal of the Korean Society of Radiology
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• v.5 no.6
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• pp.401-407
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• 2011

The purpose of this study is to know the differences of MR spectra, obtained from normal volunteers by variable TE value, through the quantitative analysis of brain metabolites by peak integral and SNR between 1.5T and 3.0T, together with PRESS and STEAM pulse sequence. Single-voxel MR proton spectra of the human brain obtained from normal volunteers at both 3.0T MR system (Magnetom Trio, SIEMENS, Germany) and 1.5T MR system (Signa Twinspeed, GE, USA) using the STEAM and PRESS pulse sequence. 10 healthy volunteers (3.0T:3 males, 2 females; 1.5T : 3 males, 2 females) with the range from 22 to 30 years old (mean 26 years) participated in our study. They had no personal or familial history of neurological diseases and had a normal neurological examination. Data acquisition parameters were closely matched between the two field strengths. Spectra were recorded in the white matter of the occipital lobe. Spectra were compared in terms of resolution and signal-to-noise ratio(SNR), and echo time(TE) were estimated at both field strengths. Imaging parameters was used for acquisition of the proton spectrum were as follow : TR 2000msec, TE 30ms, 40ms, 50ms, 60ms, 90ms, 144ms, 288ms, NA=96, VOI=$20{\times}20{\times}20mm3$. As the echo times were increased, the spectra obtained from 3.0T and 1.5T show decreased peak integral and SNR at both pulse sequence. PRESS pulse sequence shows higher SNR and signal intensity than those of STEAM. Especially, Spectra in normal volunteers at 3.0T demonstrated significantly improved overall SNR and spectral resolution compared to 1.5T(Fig1). The spectra acquired at short echo time, 3T MR system shows a twice improvement in SNR compared to 1.5T MR system(Table. 1). But, there was no significant difference between 3.0Tand 1.5T at long TE It is concluded that PRESS and short TE is useful for quantification of the brain metabolites at 3.0T MRS, our standardized protocol for quantification of the brain metabolites at 3.0T MRS is useful to evaluate the brain diseases by monitoring the systematic changes of biochemical metabolites concentration in vivo.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.421-429
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• 2005

Purpose: It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with $[^{11}C]raclopride$. Materials and Methods: Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of $24.4{\pm}1.7$ years) were enrolled in this study $[^{11}C]raclopride$, a dopamine D2 receptor radioligand, was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes ($3{\times}20s,\;2{\times}60s,\;2{\times}120s,\;1{\times}180s\;and\;22{\times}300s$). following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar)/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. Results: The mean decrease in binding potential of $[^{11}C]raclopride$ between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7%, 4.0% and 7.8%, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, p=0.04). Conclusion: These data demonstrate that in vivo imaging with $[^{11}C]raclopride$ PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount or nicotine administered bt smoking.