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Association of Estrogen Receptor Alpha and Interleukin 6 Polymorphisms with Lymphovascular Invasion, Extranodal Extension, and Lower Disease-Free Survival in Thai Breast Cancer Patients

  • Sa-Nguanraksa, Doonyapat;Suntiparpluacha, Monthira;Kulprom, Anchalee;Kummalue, Tanawan;Chuangsuwanich, Tuenjai;Avirutnan, Panissadee;O-Charoenrat, Pornchai
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2935-2940
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    • 2016
  • Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients.

Inhibition effects of extracts and its solvent fractions isolated from Limonium tetragonum on growth of human cancer cells (염생식물 갯질경 [Limonium tetragonum]의 추출물이 암세포성장에 미치는 효과)

  • Kong, Chang-Suk;Um, Young-Ran;Lee, Jung-Im;Kim, You-Ah;Lee, Jeom-Sook;Seo, Young-Wan
    • KSBB Journal
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    • v.23 no.2
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    • pp.177-182
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    • 2008
  • In this study, crude extracts of the halophyte Limonium tetragonum and their solvent fractions were evaluated on anticancer activity in AGS and HT-29 human cancer cells using MTT assay. Each of the crude extracts (MeOH and $CH_2Cl_2$) of Limonium tetragonum showed a significant inhibitory effect on the growth of human cancer cells. The combined crude extracts of MeOH and $CH_2Cl_2$ were partitioned between $CH_2Cl_2$ and water. The organic layer was further partitioned between 85% aq. MeOH and n-hexane, and then the aqueous layer was fractionated with n-BuOH and $H_2O$, successively. Growth inhibition effects of crude extracts and their solvent fractions from Limonium tetragonum increased in a dose-dependent manner. Among them, 85% aq. MeOH, n-hexane and n-BuOH fractions revealed very good inhibition effects on the growth of human cancer cells. These results suggest that we can isolate active compounds from Limonium tetragonum to show much more strong anticancer activity.

Development of Assay Methods for Enterotoxin of Escherichia coli Employing the Hybridoma Technology (잡종세포종기법을 이용한 대장균의 장독소 측정법 개발)

  • Kim, Moon-Kyo;Cho, Myung-Je;Park, Kyung-Hee;Lee, Woo-Kon;Kim, Yoon-Won;Choi, Myung-Sik;Park, Joong-Soo;Cha, Chang-Yong;Chang, Woo-Hyun;Chung, Hong-Keun
    • The Journal of the Korean Society for Microbiology
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    • v.21 no.1
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    • pp.151-161
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    • 1986
  • In order to develop sensitive and sepcific assay methods for E. coli heat labile enterotoxin(LT) hybridoma cell lines secreting LT specific monoclonal antibody were obtained. LT was purified from cell lysate of E. coli O15H11. The steps included disruption of bacteria by French pressure, DEAE Sephacel ion exchange chromatography, Sephadex G200 gel filtration, and second DEAE Sephacel ion exchange chromatography, successively. Spleen cells from Balb/c mice immunized with the purified LT and $HGPRT^{(-)}$ plasmacytomas, $P3{\times}63Ag8.V653$ were mixed and fused by 50% (w/v) PEG. Hybrid cells were grown in 308 wells out of 360 wells, and 13 wells out of them secreted antibodies reacting to LT. Among these hybridoma cell 1G8-1D1 cell line was selected since it had produced high-titered monoclonal antibody continuously. By using culture supernatant and ascites from 1G8-1D1 cells the monoclonal antibody was characterized, and an assay system for detecting enterotoxigenic E. coli was established by double sandwich enzyme-linked immunosorbent assay (ELISA). The following results were obtained. 1. Antibody titers of culture supernatant and ascites from 1G8-1D1 hybridoma cells were 512, and 102, 400, respectively by GM1-ELISA and its immunoglobulin class was IgM. 2. The maximum absorption ratio of 1G8-1D1 cell culture supernatant to LT was 90% at $300\;{\mu}g/ml$ of LT concentration. LT concentration shown at 50% absorption ratio was $103.45{\mu}g$ and the absorption ratio was decreased with tile reduction of LT concentration. This result suggests that monoclonal antibody from 1G8-1D1 hybridoma cell bound with LT specifically. 3. The reactivities of 1G8-1D1 cell culture supernatant to LT and V. cholerae enterotoxin(CT) were 0.886 and 0.142(O.D. at 492nm) measured by the GM1-ELISA, indicating 1G8-1D1 monoclonal antibody reacted specifically with LT but not with CT. 4. The addition of 0.1ml of ascites to 0.6mg and 0.12mg of LT decreased the vascular permeability factor to 41% and 44% respectively, but it did not completely neutralize LT. 5. By double sandwich ELISA using monoclonal antibody, as little as 75ng of the purified LT per ml could be detected. 6. The results by assay of detecting LT in culture supernatants of 14 wild strains E. coli isolated from diarrhea patients by the double sandwich ELISA were almost the same level as those by reverse passive latex agglutination.

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Antibacterial Activities of Bamboo Sap Against Salmonella Typhimurium and Inhibitory Effects in a Model Food System (죽력의 Salmonella typhimurium 등에 대한 항세균 활성과 Model Food System에서의 생육억제 효과)

  • Chung, Hee-Jong;Ko, Bong-Guk
    • Journal of the Korean Society of Food Culture
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    • v.20 no.6
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    • pp.709-714
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    • 2005
  • Antibacterial activities of the freeze-dried bamboo sap dissolved into the water or 50% ethanol were determined and antimicrobial activity of bamboo sap dissolved into distilled water was most strong with 15 mm of the diameter of inhibiting clear zone against Listeria monocytogenes ATCC 19114 among gram positive bacteria tested, but it did not inhibit Bacillus subtilis ATCC 6633 at all, and the sap was most greatly inhibited the growth of Shigella dysenteriae ATCC 9361 among gram negative bacteria with 15 mm of the diameter of inhibiting clear zone. Bamboo sap dissolved into 50% ethanol most strongly inhibited the growth of L. monocytogenes ATCC 19114 and it also inhibited the growth of B. subtilis ATCC 6633 which did not show any with the sap dissolved into distilled water. The sap dissolved into 50% ethanol was most greatly inhibited the growth of S. dysenteriae ATCC 9361 among gram negative bacteria with 23 mm of the diameter of inhibiting clear zone, and it inhibited Vibrio parahaemolyticus WSDH 22, Vibrio vulnilicus ATCC 29307 and Escherichia coli O157 WSDH 54 with 16 mm of the diameter of inhibiting clear zone. However, Both of the saps dissolved in distilled water and 50% ethanol did not showed any inhibition against the lactic acid bacteria of Lactobacillus plantarum KCTC and Lactobacillus brevis KCTC. Most of the tested bacteria were more sensitive to the sap dissolved in 50% ethanol than the sap dissolved in distilled water. The lowest minimum inhibitory concentration of the bamboo sap dissolved into 50% ethanol was 0.6 mg eq./disc with L. monocytogenes ATCC 19114, but that of the sap dissolved into distilled water was 0.8 mg eq./disc with Staphylococcus epidermides ATCC 12228, S. dysenteriae ATCC 9361, L. monocytogenes ATCC 19114, Salmonella typhimurium WSU 2380 and V. parahaemolyticus WSDH 22. In a model food system of the sterilized chocolate milk, antibacterial activities of the sap dissolved into 50% ethanol were relatively stronger than those of the sap dissolved into distilled water and the activities against the bacteria tested were very similar each other. These result suggested the bamboo sap can be used as a natural food preservative.

Identification of Advanced Argillic-altered Rocks of the Haenam Area, Using by ASTER Spectral Analysis (ASTER 분광분석을 통한 해남지역 강고령토변질 암석의 식별)

  • Lee, Hong-Jin;Kim, Eui-Jun;Moon, Dong-Hyeok
    • Economic and Environmental Geology
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    • v.44 no.6
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    • pp.463-474
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    • 2011
  • The Haenam epithermal mineralized zone is located in the southwestern part of South Korea, and hosts low sulfidation epithermal Au-Ag deposit (Eunsan-Moisan) and clay quarries (Okmaesan, Seongsan, and Chunsan). Epithermal deposits and accompanying hydrothermal alteration related to Cretaceous volcanism caused large zoned assemblages of hydrothermal alteration minerals. Advanced argillic-altered rocks with mineral assemblages of alunite-quartz, alunite-dickite-quartz, and dickite-kaolinite-quartz exposed on the Okmaesan, Seongsan, and Chunsan area. Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), with three visible and near infrared bands, six shortwave infrared bands, and five thermal infrared bands, was used to identify advanced argillic-altered rocks within the Haenam epithermal mineralized zone. The distinct spectral features of hydrothermal minerals allow discrimination of advanced argillic-altered rocks from non-altered rocks within the study area. Because alunite, dickite, and kaolinite, consisting of advanced argillic-altered rocks within the study area are characterized by Al-O-H-bearing minerals, these acid hydrothermal minerals have a strong absorption feature at $2.20{\mu}m$. The band combination and band ratio transformation cause increasing differences of DN values between advanced argillic-altered rock and non-altered rock. The alunite and dickite-kaolinite of advanced argillic-altered rocks from the Okmaesan, Seongsan, and Chunsan have average DN values of 1.523 and 1.737, respectively. These values are much higher than those (1.211 and 1.308, respectively) of non-altered area. ASTER images can remotely provide the distribution of hydrothermal minerals on the surface. In this way good relation between ASTER spectra analysis and field data suggests that ASTER spectral analysis can be useful tool in the initial steps of mineral exploration.

The Geochemistry of Copper-bearing Hydrothermal Vein Deposits in Goseong Mining District (Samsan Area), Gyeongsang Basin, Korea (경상분지내 삼산지역 열수동광상에 관한 지화학적 연구)

  • Choi, Sang Hoon;So, Chil Sup;Kweon, Soon Hag;Choi, Kwang Jun
    • Economic and Environmental Geology
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    • v.27 no.2
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    • pp.147-160
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    • 1994
  • Copper-bearing hydrothermal vein mineralization of the Samsan area was deposited in two stages (I and II) of quartz-calcite-sulfide veins which fill fissures in Cretaceous volcanic and sedimentary rocks of the Gyeongsang basin. The major ore minerals, chalcopyrite and sphalerite, together with pyrite, galena, hematite, and minor sulfosalts, occur with epidote and chlorite as gangue minerals in stage I quartz veins. Chlorite geothermometry, fluid inclusion and stable isotope data indicate that copper ore was deposited mainly at temperatures between $330^{\circ}C$ and $280^{\circ}C$ from fluids with salinities between 12 and 3 equiv. wt % NaCl. Evidence of fluid boiling indicates a range of pressures from ${\leq}100$ to 200 bars bars. Within ore stage I there was an apparent decrease in ${\delta}^{34}S$ values of $H_{2}S$ with paragenetic time, from 8.0 to 2.3 per mil. This pattern was likely achieved through progressive increases in activity of oxygen accompanying boiling and mixing. In the early part of the first stage, the high temperature, high salinity fluids gave way to progressively cooler and more dilute fluids of the late parts in the first stage and of the second stage. There is a systematic decrease in calculated ${\delta}^{18}O_{water}$ values with decreasing temperature in the Samsan hydrothermal system, from values of -86 per mil for early portion of stage I through -5.9 per mil for late portion of stage I to -6.3 per mil for stage II. The ${\delta}D$ values of fluid inclusion waters also decrease with paragenetic time from -76 per mil to -86 per mil. These trends combined with mineral paragenesis and fluid inclusion data are interpreted to indicate progressive cooler, more oxidizing meteoric water inundation of an early exchanged meteoric hydrothermal system.

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Effect of a Combined Treatment with Uniconazole, Silver Thiosulfate on Reduction of Ozone Injury in Tomato Plant (Uniconazole 과 Silver Thiosulfate 의 복합처리가 토마토의 오존피해경감에 미치는 효과)

  • Ku, Ja-Hyeong;Won, Dong-Chan;Kim, Tae-Il;Krizek, Donld T.;Mirecki, Roman M.
    • Korean Journal of Environmental Agriculture
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    • v.11 no.1
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    • pp.50-58
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    • 1992
  • Studies were conducted to determine the combined effect of uniconazole [(E) -1-(4-chlorophenyl)-4, 4-demethyl 2-(1,2,4 triazol-1-yl)-1-penten-3-ol] and silver thiosulfate $[Ag {(S_2O_3)}^3\;_2-]$ (STS) on reduction of ozone injury in tomato plants(Lycopersicon esculentum Mill. 'Pink Glory'). Plants were given a 50ml soil drench of uniconazole at concentrations of 0, 0.001, 0.01 and 0.1 mg/pot at the stage of emerging 4th leaf. Two days prior to ozone fumigation, STS solution contained 0.05% Tween-20 was also sprayed at concentrations of 0, 0.3 and 0.6 mM. Uniconazole at 0.01 mg/pot and STS at 0.6 mM were effective in providing protection against ozone exposure(20h at 0.2ppm) without severe retardation of plant height and chemical phytotoxicity, respectively. Combined treatment with uniconazole, STS significantly reduced ozone injury at the lower concentration than a single treatment with uniconazole or STS. Uniconazole treatment reduced plant height, stem elongation and transpiration rate on a whole plant level and increased chlorophyll concentration. STS did not give any effect on plant growth and chlorophyll content but increased transpiration rate in non-ozone-fumigated plants. Ethylene production in the leaves of ozone-fumigated plants was decreased by uniconazole and STS pretreatment, but there was no protective effect on epinasty of leaves in uniconazole-treated plants. STS increased ethylene production in non-ozone-fumigated plants, but it significantly reduced the degree of epinasty and defoliation of cotyledons when plants were exposed to ozone. Uniconazole slightly increased superoxide dismutase and peroxidase activities. But STS showed little or no effects on such free radical scavengers. Day of flowering after seeding was shortened and percentages of fruit set were increased by uniconazole treatment. STS was highly effective on protecting reduction of fruit set resulting from ozone fumigation. These results suggest that combined use of uniconazole and STS should provide miximum protection against ozone injury without growth retardation resulting in yield loss.

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Carbon nanotube field emission display

  • Chil, Won-Bong;Kim, Jong-Min
    • Electrical & Electronic Materials
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    • v.12 no.7
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    • pp.7-11
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    • 1999
  • Fully sealed field emission display in size of 4.5 inch has been fabricated using single-wall carbon nanotubes-organic vehicle com-posite. The fabricated display were fully scalable at low temperature below 415$^{\circ}C$ and CNTs were vertically aligned using paste squeeze and surface rubbing techniques. The turn-on fields of 1V/${\mu}{\textrm}{m}$ and field emis-sion current of 1.5mA at 3V/${\mu}{\textrm}{m}$ (J=90${\mu}{\textrm}{m}$/$\textrm{cm}^2$)were observed. Brightness of 1800cd/$m^2$ at 3.7V/${\mu}{\textrm}{m}$ was observed on the entire area of 4.5-inch panel from the green phosphor-ITO glass. The fluctuation of the current was found to be about 7% over a 4.5-inch cath-ode area. This reliable result enables us to produce large area full-color flat panel dis-play in the near future. Carbon nanotubes (CNTs) have attracted much attention because of their unique elec-trical properties and their potential applica-tions [1, 2]. Large aspect ratio of CNTs together with high chemical stability. ther-mal conductivity, and high mechanical strength are advantageous for applications to the field emitter [3]. Several results have been reported on the field emissions from multi-walled nanotubes (MWNTs) and single-walled nanotubes (SWNTs) grown from arc discharge [4, 5]. De Heer et al. have reported the field emission from nan-otubes aligned by the suspension-filtering method. This approach is too difficult to be fully adopted in integration process. Recently, there have been efforts to make applications to field emission devices using nanotubes. Saito et al. demonstrated a car-bon nanotube-based lamp, which was oper-ated at high voltage (10KV) [8]. Aproto-type diode structure was tested by the size of 100mm $\times$ 10mm in vacuum chamber [9]. the difficulties arise from the arrangement of vertically aligned nanotubes after the growth. Recently vertically aligned carbon nanotubes have been synthesized using plasma-enhanced chemical vapor deposition(CVD) [6, 7]. Yet, control of a large area synthesis is still not easily accessible with such approaches. Here we report integra-tion processes of fully sealed 4.5-inch CNT-field emission displays (FEDs). Low turn-on voltage with high brightness, and stabili-ty clearly demonstrate the potential applica-bility of carbon nanotubes to full color dis-plays in near future. For flat panel display in a large area, car-bon nanotubes-based field emitters were fabricated by using nanotubes-organic vehi-cles. The purified SWNTs, which were syn-thesized by dc arc discharge, were dispersed in iso propyl alcohol, and then mixed with on organic binder. The paste of well-dis-persed carbon nanotubes was squeezed onto the metal-patterned sodalime glass throuhg the metal mesh of 20${\mu}{\textrm}{m}$ in size and subse-quently heat-treated in order to remove the organic binder. The insulating spacers in thickness of 200${\mu}{\textrm}{m}$ are inserted between the lower and upper glasses. The Y\ulcornerO\ulcornerS:Eu, ZnS:Cu, Al, and ZnS:Ag, Cl, phosphors are electrically deposited on the upper glass for red, green, and blue colors, respectively. The typical sizes of each phosphor are 2~3 micron. The assembled structure was sealed in an atmosphere of highly purified Ar gas by means of a glass frit. The display plate was evacuated down to the pressure level of 1$\times$10\ulcorner Torr. Three non-evaporable getters of Ti-Zr-V-Fe were activated during the final heat-exhausting procedure. Finally, the active area of 4.5-inch panel with fully sealed carbon nanotubes was pro-duced. Emission currents were character-ized by the DC-mode and pulse-modulating mode at the voltage up to 800 volts. The brightness of field emission was measured by the Luminance calorimeter (BM-7, Topcon).

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Radiosynthesis of $[^{11}C]6-OH-BTA-1$ in Different Media and Confirmation of Reaction By-products. ($[^{11}C]6-OH-BTA-1$ 조제 시 생성되는 부산물 규명과 반응용매에 따른 표지 효율 비교)

  • Lee, Hak-Jeong;Jeong, Jae-Min;Lee, Yun-Sang;Kim, Hyung-Woo;Lee, Eun-Kyoung;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.3
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    • pp.241-246
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    • 2007
  • Purpose: $[^{11}C]6-OH-BTA-1$ ([N-methyl-$^{11}C$]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole, 1), a -amyloid imaging agent for the diagnosis of Alzheimer's disease in PET, can be labeled with higher yield by a simple loop method. During the synthesis of $[^{11}C]1$, we found the formation of by-products in various solvents, e.g., methylethylketone (MEK), cyclohexanone (CHO), diethylketone (DEK), and dimethylformamide (DMF). Materials and Methods: In Automated radiosynthesis module, 1 mg of 4-aminophenyl-6-hydroxybenzothiazole (4) in 100 l of each solvent was reacted with $[^{11}C]methyl$ triflate in HPLC loop at room temperature (RT). The reaction mixture was separated by semi-preparative HPLC. Aliquots eluted at 14.4, 16.3 and 17.6 min were collected and analyzed by analytical HPLC and LC/MS spectrometer. Results: The labeling efficiencies of $[^{11}C]1$ were $86.0{\pm}5.5%$, $59.7{\pm}2.4%$, $29.9{\pm}1.8%$, and $7.6{\pm}0.5%$ in MEK, CHO, DEK and DMF, respectively. The LC/MS spectra of three products eluted at 14.4, 16.3 and 17.6 mins showed m/z peaks at 257.3 (M+1), 257.3 (M+1) and 271.3 (M+1), respectively, indicating their structures as 1, 2-(4'-aminophenyl)-6-methoxybenzothiazole (2) and by-product (3), respectively. Ratios of labeling efficiencies for the three products $([^{11}C]1:[^{11}C]2:[^{11}C]3)$ were $86.0{\pm}5.5%:5.0{\pm}3.4%:1.5{\pm}1.3%$ in MEK, $59.7{\pm}2.4%:4.7{\pm}3.2%:1.3{\pm}0.5%$ in CHO, $9.9{\pm}1.8%:2.0{\pm}0.7%:0.3{\pm}0.1%$ in DEK and $7.6{\pm}0.5%:0.0%:0.0%$ in DMF, respectively. Conclusion: The labeling efficiency of $[^{11}C]1$ was the highest when MEK was used as a reaction solvent. As results of mass spectrometry, 1 and 2 were conformed. 3 was presumed.