• The Korean Journal of Nuclear Medicine
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• v.33 no.6
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• pp.527-536
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• 1999

Purpose: Radiotracers that bind to the central benzodiazepine receptor are useful for the investigation of various neurological and psychiatric diseases. [C-11]Flumazenil, a benzodiazepine antagonist, is the most widely used radioligand for central benzodiazepine receptor imaging by PET. We synthesized 3-(2-[F-18]fluoro)flumazenil, a new fluorine-18 ($t_{1/2}$= 110 min) labeled analogue of benzodiazepine receptor imaging agent, and evaluated in vivo for biodistribution in mice. Materials and Methods: Flumazenil (Ro 15-1788) was synthesized by a modification of the reported method. Precursor of 3-(2-[F-18]fluoro)flumazenil, the tosylated flumazenil derivative was prepared by the tosylation of the ethyl ester by ditosylethane. [F-18] labeling of tosyl substitued flumazenil precursor was performed by adding F-18 ion at $85^{\circ}C$ in the hot ceil for 20 min. The reaction mixture was trapped by C18 cartridge, washed with 10% ethanol, and eluted by 40% ethanol. Bidistribution in mice was determined after intravenous injection. Results: The total chemical yield of tosylated flumazenil derivative was ${\sim}40%$. The efficiency of labeling 3-(2-[F-18]fluoro)flumazenil was 66% with a total synthesis time of 50 min. Brain uptakes of 3-(2-[F-18]fluoro)flumazenil at 10, 30, 60 min after injection, were $2.5{\pm}0.37,\;2.2{\pm}0.26,\;2.1{\pm}0.11$ and blood activities were $3.7{\pm}0.43,\;3.3{\pm}0.07,\;3.3{\pm}0.09%ID/g$, respectively. Conclusion: We synthesized a tosylated flumazenil derivative which was successfully labeled with no-carrier-added F-18 by nucleophilic substitution.

• Journal of Haehwa Medicine
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• v.24 no.2
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• pp.35-57
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• 2016

Objectives : The purpose of this study is to prove the effect and mechanism of Gamikyejakjimogawusul-tang(GKHA) herbal acupuncture on induced rheumatoid arthritis model of DBA/1 mice. Methods : We check effect of GKHA extract on the AST, ALT, Creatinine, BUN of serum and cell viability of GK extract in RAW 264.7 cells to test the stability of this study. In vitro, we measure total phenol contents, total flavonoid contents, DPPH free radical scavenging activity, ABTS cation radical scavenging activity of Gamikyejakjimogawusul-tang, effect of GK extract on ROS(Reactive Ooxygen Species) production to estimate a anti-oxidant capacity, and we also measure effect of GK extract on NO (Nitric Oxid), IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF production in RAW 264.7 cells to estimate a anti-inflammatory efficacy. In vivo, we compare a rheumatoid arthritis manifestation between control and experimental group and estimate a AI. Then we check effect of GKHA on the level of WBC, neutrophil, lympocyte, monocyte in the blood to see the effect of immune cells in blood. In addition we measure effect of GKHA on the level of hs-CRP, IgM, IgG, IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF in serum. We observe effects of GKHA on imaging of cartilage degeneration using micro CT-arthrography in paw hind. And we calculate effects of GKHA that reduced BV ratio, BS/BV ratio using 3D Micro-CT. Lastly we observe effects of GKHA histopathologic examination analysis. Results : 1. The toxicity on liver and kidney was disregardable and the cytotoxicity against RAW 264.7 cells was also disregardable. 1. Total phenol contents and total flavonoid contents in GK extract were in high level. 2. DPPH free radical scavenging activity and ABTS cation radical scavenging activity were increased according to concentration of GK extract 3. ROS production was significantly decreased in GK extract (at 10, $100{\mu}g/ml$). 4. NO, IL-6, TNF-${\alpha}$, MCP-1 production were significantly decreased in GK extract(at 10, $100{\mu}g/ml$). IL-17, GM-CSF production were significantly decreased in GK extract(at 1, 10, $100{\mu}g/ml$). IL-$1{\beta}$, IL-21 production were also decreased but there was no statistical significance. 5. 25x observation after H&E and M-T staining, infiltration of immune cells and subsidence of the cartilage and damage to the synovial cells were decreased. Conclusions : This study showed that GKHA extract had anti-oxidant capacity, anti-inflammatory efficacy. GKHA extract also had inhibiting effect on the process of rheumatoid arthritis and can protect joint and cartilage. So we expect that GKHA extract can be a meaningful treatment to rheumatoid arthritis patients.

• Microbiology and Biotechnology Letters
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• v.31 no.4
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• pp.377-382
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• 2003

Purification of methioninase resulted in a yield of 69%, and SDS-PAGE analysis of the purified product revealed a single band of approximately 43 kDa in molecular weight. in vitro experiments with cancer cells incubated in methionine-free media demonstrated an increase in $^{11}$ C-methionine uptake to 25.8$\pm$1.1% at 6 hr, 31.8$\pm$0.8% at 24 hr, and 62.2$\pm$0.6% at 48hr, compared to controls. Treatment of the cancer cells with purified methioninase showed no decrease in survival after a 2 hr incubation with 0.01 U/ml, but survival of RR1022 cells decreased 30% after 24 to 48 hr incubation. SKOV-3 cells showed a 5% and 14% decrease in survival with 0.1 and 1 U/ml methioninase after 24 hr. After 48hr survival decreased 15% and 24% with 0.1 and 1 U/ml methioninase. Measurements of $^{11}$ C-methionine uptake in RR1022 cells demonstrated no change at 2 hr, but a 13.7$\pm$4.7% and 40.7$\pm$2.6% increase in uptake at 24 and 48 hr, respectively. SKOV-3 cells also showed no change at 2 hr, but had a 17.7$\pm$7.2% and 38.9$\pm$4.9% increase in $^{11}$ C-methionine uptake after 24 hr and 48 hr treatment with methioninase, respectively. $^{11}$ C-methionine PET imaging revealed clear visualization of both the tumors and contralateral infectious lesions. Administration of rMET appeared to result in a slight increase in tumor:nontumor contrast on $^{11}$ C-methionine PET images. Injection of purified methioninase also produced PET images where tumor uptake was higher than that of infectious lesions.

• Progress in Medical Physics
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• v.23 no.3
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• pp.162-168
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• 2012

In proton therapy, in vivo dose verification is one of the most important parts to fully utilize characteristics of proton dose distribution concentrating high dose with steep gradient and guarantee the patient safety. Currently, in order to image the proton dose distribution, a prompt gamma distribution detection system, which consists of an array of multiple CsI(Tl) scintillation detectors in the vertical direction, a collimator, and a multi-channel DAQ system is under development. In the present study, the optimal design of prompt gamma distribution detection system was studied by Monte Carlo simulations using the MCNPX code. For effective measurement of high-energy prompt gammas with enough imaging resolution, the dimensions of the CsI(Tl) scintillator was determined to be $6{\times}6{\times}50mm^3$. In order to maximize the detection efficiency for prompt gammas while minimizing the contribution of background gammas generated by neutron captures, the hole size and the length of the collimator were optimized as $6{\times}6mm^2$ and 150 mm, respectively. Finally, the performance of the detection system optimized in the present study was predicted by Monte Carlo simulations for a 150 MeV proton beam. Our result shows that the detection system in the optimal dimensions can effectively measure the 2D prompt gamma distribution and determine the beam range within 1 mm errors for 150 MeV proton beam.

• The Korean Journal of Nuclear Medicine
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• v.39 no.1
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• pp.34-43
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• 2005

Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of $^{99m}Tc$-MIBI and $^{99m}Tc$-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. Results: RT-PCR, western blot analysis of the cells and irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.

• Progress in Medical Physics
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• v.13 no.4
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• pp.224-228
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• 2002

Myocardial tagging technique such as spatial modulation of magnetization (SPAMM) allows the study of myocardial motion with high accuracy. However, the accuracy of the estimation of tag intersection can be affected by tagline spacing. The aim of this study was to investigate the relationship between tagline spacing of SPAMM image and tagging contrast-to-noise ratio (CNR) in in-vivo study. Two healthy volunteers were undergone electrocardiographically triggered MR imaging with SPAMM-based tagging pulse sequence at a 1.5T MR scanner. Horizontally modulated stripe patterns were imposed with a range from 3.6 to 9.6 mm of tagline spacing. Images of the left ventricle(LV) wall were acquired at the mid-ventricle level during cardiac cycle with FE-EPI (TR/TE = 5.8/2.2 msec, FA= 10$^{\circ}$. Tagging CNR for each image was calculated with a software which developed in our group. During contraction, tagging CNR was more rapidly decreased in case of narrow tagline spacing than in case of wide tagline spacing. In the same heart phase, CNR was increased corresponding with tagline spacing. Especially, at the fully contracted heart phase, CNR was more rapidly increased than the other heart phases as a function of tagline spacing. The results indicated that the optimization of tagline spacing provides better tagging CNR in order to analyze the myocardial motion more accurately.

• The Korean Journal of Nuclear Medicine Technology
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• v.23 no.2
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• pp.25-28
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• 2019

Purpose In patients with unusual kidney position after $^{99m}Tc-DTPA$ renal dynamic imaging study, the GFR(Glomerular Filtration Rate) values are significantly different according to the depth of the kidney. Thus, we tried to compare the difference of the GFR values between the depth measurement methods and in-vitro test. 30 adult patients who were subjected to renal study. 27 patients were in usual position and 3 patients were in unusual. $555{\pm}37MBq$ of $^{99m}Tc-DTPA$ was administrated to all patients. GE infinia gamma camera was used. GFR values were obtained in-vivo(gates method) and in-vitro(blood). The kidney depth in-vivo was calculated by three methods(tonnensen, manual, taylor). In-vitro, GFR was performed by blood test. Differences in the mean values of GFR and correlation between depth and GFR values were evaluated using the SPSS 12.0 statistical program. The GFR values for 27 patients with kidney in the usual position are as follows(1.tonnensen 2.manual 3.taylor 4.invitro); $69.3{\pm}4.2$, $88.2{\pm}5.6$, $77.8{\pm}4.3$, $82.2{\pm}5.8ml/min$. The three unusual cases are as follows, first(congenital renal anomaly): 66.4, 101.24, 69.07, 94.8 ml/min. second(transplantation kidney): 12.22, 29.99, 19.36, 23.5 ml/min. third(horseshoe kidney): 37.37, 93.54, 35.9, 92.5 ml/min. There was a difference between tonnensen and manual in the usual position of the kidney(p<0.05). There was no significant difference between the other methods. However, there was a significant difference in case of the unusual position of the kidneys. Correlation analysis between both kidney depth and GFR value shows person correlation as follows; Rt kidney: 0.298, Lt kidney: 0.322. When compared with the GFR values in-vitro test, it was useful to calculate the GFR value by measuring the kidney depth using a manual formula in the unusual position of the kidneys. GFR values and kidney depth were significantly related.

• The Journal of Korean Physical Therapy
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• v.18 no.6
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• pp.1-11
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• 2006

Purpose: This study compared the effects of non-cold and cold conditions on the viscoelastic properties of tendon structures in vivo. Methods: Seven male subjects perfomed plantar flesion exercise with maximal isokinetic voluntary contraction, which consisted of muscle contraction for 6 see and relaxation for 60 secs, 10 times for 1 set, Totally 10 sets were repeated. Before and after each task, the elongation of the tendon and aponeurosis of the medial gastrocnemius muscle (MG) was directly measured by ultrasonography. (The relationship between the estimated tendon force and tendon elongation.) Tendon cross-sectional area and ankle joint moment arm were obtained from magnetic resonance imaging (MRI). The tendon force was calculated from the joint moments and the tendon moment arm and stress was obtained by dividing force by cross-sectional areas (CSA). The strain was measured from the displacements normalized to tendon length. Results: After cooling, the tendon force was larger in cold than non-cold. The value of the tendon stiffness of MVC were significantly higher under the cold condition than under the non-cold condition. The maximal strain and stress of $7.4{\pm}0.7%$ and $36.4{\pm}1.8$ MPa in non-cold and $7.8{\pm}8.5%,\;31.8{\pm}1.1$ MPa in cold (P<0.05). Conclusion: This study shows for the first time that the muscle endurance in cooling increases the stiffness and Young's modulus of human tendons. The improvement in muscle endurance with cooling was directly related to muscle and tendon.

• The Korean Journal of Nuclear Medicine
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• v.39 no.5
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• pp.278-283
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• 2005

Purpose: In prior study, we synthesized $^{99m}Tc$-galactosylated chitosan (GC) and performed in vivo biodistribution study, showed specific targeting to hepatocyte. The aim of this study is to evaluate the labeling efficiency and cytotoxicity of modified galactosylated chitosan compounds, galactosyl methylated chitosan (GMC) and HYNIC-galactosylated chitosan (GCH). Materials and Methods: GC, GMC and GCH were synthesized and radiolabeled with $^{99m}Tc$. Then, they were incubated for 6 hours at room temperature and human serum at $37^{\circ}C$. Labeling efficiencies were determined at 15, 30 m, 1, 2, 3 and 6 h after radiolabeling. To evaluate cytotoxicity, MTT assay was performed in HeLa and HepG2 cells. Results: In comparison with them of $^{99m}Tc$-GC labeling efficiencies of $^{99m}Tc$-GMC were significantly improved (100, 97 and 89%) in acetone and 96.3, 95.8 and 75.6% in saline at 15 m, 1 and 6 h, respectively). Moreover, $^{99m}Tc$-GCH showed more improved labeling efficiencies (>95% in acetone and human serum and >90% in saline at 6 h). In MTT assay, cytotoxicity was very low and not different from that of controls. Conclusion: These results represent that these compounds are radiochemically compatible radiopharmaceuticals, can be used in hepatocyte specific imaging study and in vivo gene or drug delivery monitoring.

• The Korean Journal of Nuclear Medicine
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• v.25 no.2
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• pp.286-293
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• 1991

$^{123}I$, which is applied for the thyroid and other in vivo kinetic study, has a special role in life sciences. The 159 KeV $\gamma-ray$ from $^{123}I$ is almost ideally appropriate for the current imaging instrumentation. Its decay mode (electron capture) and short half-life (13.3 hr) reduced the burden of radiation dose to the patients, and its chemical property makes it easy to synthesize the labelling compounds. In this experiment, the production of $^{123}I$ via the nuclear reaction $^{124}Te(p,2n)^{123}I$ with 28 MeV protons was sutdied. $TeO_2$ is used as a target material, because it has good physical properties. The target was prepared with $TeO_2$ powder and was molten into a ellipsoidal cavity (a=14 mm, b=10 mm, $270.8mg/cm^2$ thick) of pure platinum. The irradiation was carried out in the external proton beam with incident energies range from 28 MeV to 22 MeV, and current was $30{\mu}A$. The loss of $TeO_2$ target was significantly reduced by using $4\pi-cooling$ system in irradiation. The dry distillation method was adopted for the separation of $^{123}I$ from irradiated target, and when it was kept 5 minutes at $780^{\circ}C$, its result was quantitative. The loss of the target material $(TeO_2)$ was below 0.2% for each production run and $^{123}I$ from the dry distillation apparatus was captured with 0.01 N NaOH in $Na^{123}I$ form, then the pH of the solution was adjusted to $7.5\sim9.0$ with HC1/NaOH. The $Na^{123}I$ solution was passed through $0.2{\mu}m$ membrane filter, and sterilized under high pressure and temperature for 30 minutes. The production of $^{123}I$ is acceptable for clinical application based on the quality of USP XXI.