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Synthesis and Preliminary Evaluation of $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$ Guanine $([^{18}F]FHBG)$ in HSV1-tk Gene Transduced Hepatoma Cell (9-(4-$[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine $([^{18}F]FHBG)$의 합성과 헤르페스 단순 바이러스 티미딘 키나아제 이입 간암 세포주에서의 기초 연구)

  • Moon, Byung-Seok;Lee, Tae-Sup;Lee, Myoung-Keun;Lee, Kyo-Chul;An, Gwang-Il;Chun, Kwon-Soo;Awh, Ok-Doo;Chi, Dae-Yoon;Choi, Chang-Woon;Lim, Sang-Moo;Cheon, Gi-Jeong
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.4
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    • pp.218-227
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    • 2006
  • Purpose: The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine ($[^{18}F]FHBG$) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Materials and Methods: Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with $K[^{18}F]/K2.2.2.$ in acetonitrile using N2-monomethoxytrityl-9-14-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of $[^{18}F]FHBG$ were performed, and was analyzed correlation between $[^{18}F]FHBG$ uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model. Results: $[^{18}F]FHBG$ was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiothemical yield was about 20-25%) (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 $GBq/{\mu}\;mol$. Specific accumulation of $[^{18}F]FHBG$ was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked $[^{18}F]FHBG$ was retained inside of cells. The uptake of $[^{18}F]FHBG$ was showed a highly significant linear correlation ($R^2=0.995$) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. Conclusion: $[^{18}F]FHBG$ appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.

Smoking-Induced Dopamine Release Studied with $[^{11}C]Raclopride$ PET ($[^{11}C]Raclopride$ PET을 이용한 흡연에 의한 도파민 유리 영상 연구)

  • Kim, Yu-Kyeong;Cho, Sang-Soo;Lee, Do-Hoon;Ryu, Hye-Jung;Lee, Eun-Ju;Ryu, Chang-Hung;Jeong, In-Soon;Hong, Soo-Kyung;Lee, Jae-Sung;Seo, Hong-Gwan;Jeong, Jae-Min;Lee, Won-Woo;Kim, Sang-Eun
    • 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.

The Comparative Imaging Study on Mn-phthalocyanine and Mangafodipir trisodium in Experimental VX2 Animal Model (실험적으로 유발시킨 VX2 동물모델에서의 Mn-phthalocyanine과 Mangafodipir trisodium의 비교영상)

  • Park Hyun-Jeong;Ko Sung-Min;Kim Yong-Sun;Chang Yongmin
    • Investigative Magnetic Resonance Imaging
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    • v.8 no.1
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    • pp.32-41
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    • 2004
  • Purpose : To measure the NMR relaxation properties of MnPC, to observe the characteristics of liver enhancement patterns on MR images in experimentally implanted rabbit VX2 tumor model, and to estimate the possibility of tissue specific contrast agent for MnPC in comparison with the hepatobiliary agent. Materials and Methods : Phthalocyanine (PC) was chelated with paramagnetic ions, manganese (Mn). 2.01 g (5.2 mmol) of phthalocyanine was mixed with 0.37 g (1.4 nlmol) of Mn chloride at $310^{\circ}C$ for 36 hours and then purified by chromatography ($CHCl_3:\;CH_3OH=98:2$, volume ratio) to obtain 1.04 g $(46\%)$ of MnPC (molecular weight = 2000 daltons). The T1/T2 relaxivity (R1/R2) for MnPC were determined at a 1.5 T (64 MHz) MR spectrometer. VX2 tumor model was experimentally implanted in the liver parenchyma of rabbits. All MR studies were performed on 1.5 T. The human extremity radio frequency coil of a bird cage type was employed. MR images were acquired at 17 to 24 days after VX2 carcinoma implantation.4 mmol/kg MnPC and 0.01 mmol/kg Mn-DPDP were injected via the ear vein of rabbits. T1-weighted images were obtained with spin-echo (TR/TE=516/14 msec) and fast multiplanar spoiled gradient recalled (TR/TE : 80/4 msec, $60^{\circ}$ flip angle) pulse sequence. Fast spin-echo (TR/TE=1200/85 msec) was used to obtain the T2-weighted images. Results : The value of T1/T2 relaxivity (R1/R2) of MnPC was $7.28\;mM^{-1}S^{-1}$ and $55.56\;mM^{-1}S^{-1}$ respectively at 1.5 T (64 MHz). Because the T2 relaxivity of MnPC that bonded strongly, covalently manganese with phthalocyanine was very high, the signal intensity of liver parenchyma was decreased on postcontrast T2-weighted images and we could easily distinguish the VX2 carcinoma within the liver parenchyma. When MnPC was administrated intravenously, the tumor margin delineation was more remarkable than Mn-DPDP-enhanced images. The enhancement of liver parenchyma with MnPC persisted at relatively high levels over at least one hour after injection of the contrast agents. Conclusion : The hepatic uptake and biliary excretion of MnPC, which are similar to Mn-DPDP, suggest that this agent is a new liver-specific agent. Also, MnPC seems to be used as a dual contrast agent (T1 and T2) with high T2 relaxivity. However, it is warranted that MnPC needs further investigation as a potential contrast agent for MR imaging of the liver. That is, further characterizations of MnPC are needed in vivo and in vitro before clinical trials. The diagnostic potential of MnPC will also have to be examined more in the animal models of additional types.

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Studies of the Effects of Acupuncture Stimulation at Huatuo Jiaji(EX B2) Points on Axonal Regeneration of Injured Sciatic Nerve in the Rats (화타협척혈 침자극에 의한 손상 말초신경의 재생효과에 관한 연구)

  • Kim, Dae-Feel;Park, Young-Hoi;Keum, Dong-Ho
    • Journal of Korean Medicine Rehabilitation
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    • v.18 no.4
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    • pp.39-61
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    • 2008
  • Objectives : The present study was performed to investigate whether acupuncture stimulation in the rats affected regeneration properties of the injured sciatic nerve. A differential effect of acupuncture stimulation on the one point near the spinal nerve root controlling sciatic nerve activity and the other point in the peripheral area subordinated by injured nerve was compared. Materials and Methods: Rat sciatic nerves were injured by crush, and the effects on axonal regeneration on injured sciatic nerves were evaluated by acupuncture stimulation at two different regions. In proximal acupuncture stimulation group, acupuncture stimulation was performed on Huatuo Jiaji(EX B2) points located from L5 to S1 vertebral levels to stimulate the nearest spinal nerve root that innervates sciatic nerves. In distal acupuncture stimulation group, acupuncture stimulation was performed on Zusanli(ST 36) and Weizhong(BL 40) points to stimulate at peripheral area dominated by injured sciatic nerves. Acupuncture stimulation was given every other days for 1 or 2 weeks. Sciatic nerve tissues collected from acupuncture stimulation experimental groups, injury control group, and intact animal group were used for protein analysis by Western blotting or Hoechst nuclear staining. To determine axonal regeneration, Dil fluorescence dye was injected into the sciatic nerve 0.5 cm distal to the injury site in individual animal groups and Dil-labeled cells by retrograde tracing were measured in the DRG at lumbar 5 or in the spinal cord. DRG sensory neurons prepared from individual animal groups were used to measure the extent of neurite outgrowth and for immunofluorescence staining with anti-GAP-43 antibody. Results : Animal groups given proximal or distal acupuncture stimulation showed upregulation of GAP-43 and Cdc2 protein levels in the sciatic nerve at 7 days after injury. Cdk2 protein levels were strongly induced by nerve injury, but did not show changes by acupuncture stimulation. Phospho-Erk1/2 protein levels were elevated by acupuncture stimulation above those present in the injury control animals. These increase in regeneration-associated protein levels appeared to be related with increase cell proliferation in the injured sciatic nerves. Hoechst 33258 staining of sciatic nerve tissue to visualize nuclei of individual cells showed increased Schwann cell number in the distal portion of the injured nerve 7 and 14 days after injury and further increases by acupuncture stimulation particularly at the proximal position. Measurement of axonal regeneration by retrograde tracing showed significantly increased Dil-labeled cells in proximal acupuncture stimulation group compared to distal acupuncture stimulation group and injury control group. Finally, an evaluation of axonal regeneration by retrograde tracing showed increased number of Dil labeled cells in the DRG at lumbar 5 or in the ventral horn of the spinal cord at lower thoracic level at 7 days after nerve injury. Conclusions : The present data show that the proximal acupuncture stimulation at Huatuo Jiaji(EX B2) points governing injured sciatic nerves was more effective for axonal regeneration than the distal acupuncture stimulation. Further studies on functional recovery or associated molecular mechanisms should be critical for developing animal models and clinical applications.

A study on the improvement of distribution system by overseas agricultural investment (해외농업투자에 따른 유통체계 개선방안에 관한 연구)

  • Sun, Il-Suck;Lee, Dong-Ok
    • Journal of Distribution Science
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    • v.8 no.3
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    • pp.17-26
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    • 2010
  • Recently concerns have been raised due to the unbalanced supply of crops: the price of crops has been unstable and at one point the price went up so high that the word Agflation(agriculture+ inflation) was coined. Korea, in particular, is a small-sized country and needs to secure the stable supply of crops by investing in the produce importation at a national level. Investment in foreign produce importation is becoming more important as a measure for sufficient supply of crops, limited supply of domestic crops, weakened farming conditions worldwide, as well as recent changes in the use of crops due to the development of bio-fuels, influence of carbon emission on crops, the price increase in crops, and influx of foreign hot money. However, there are many problems with investing in foreign produce importation: lack of support from the government; lack of farming information and technology; difficulty in securing the capital; no immediate pay-off from the investment and insufficient management. Although foreign produce is originally more price-competitive than domestic produce, it loses its competiveness in the process of importation (due to high tariffs) and poor distribution system, which makes it difficult to sell in Korea. Therefore, investment in foreign produce importation is being questioned for feasibility; to make it possible, foreign produce must maintain the price-competitiveness. Especially, harvest of agricultural products depends on natural and geographical conditions of each country and those products have indigenous properties, so distribution system according to import and export of agricultural products should be treated more carefully than that of other industries. Distribution costs are differentiated into each item and include cost of sorting and wrapping, cost of wrapping materials, cost of domestic transport, cost of international transport and cost of clearing customs for import and export. So transporting and storing agricultural products generates considerable costs compared with other products. Also, due to upgrade of dietary life, needs for stability, taste and visible quality toward food including agricultural products are being raised and wrong way of storage causes decomposition of food and loss of freshness, making the storage more difficult than that in room temperature, so storage and transport in distribution of agricultural products needs specialty. In addition, because lack of specialty in distribution and circulation such as storage and wrapping does not solve limit factors in distance, the distribution and circulation has been limited to a form of import and export within short-distant region. Therefore, need for distribution out-sourcing which can satisfy specialty in managing distribution and circulation and it is needed to establish more effective distribution system. However, existing distribution system of agricultural products is exposed to various problems including problems in distribution channel, making distribution and strategy for distribution and those problems are as follows. First, in case of investment in overseas agricultural industry, stable supply of the products is difficult because areas of production are dispersed widely and influenced by outer factors due to including overseas distribution channels. Also, at the aspect of quality, standardization of products is difficult, distribution system is quite complicated and unreasonable due to long distribution channels according to international trade and financial and institutional support is not enough. Especially, there are quite a lot of ineffective factors including multi level distribution process, dramatic gap between production cost and customer's cost, lack of physical distribution facilities and difficulties in storage and transport due to lack of wrapping containers. Besides, because import and export of agricultural products has been manages under the company's own distribution according to transaction contract between manufacturers and exporting company, efficiency is low due to excessive investment in fixed costs and lack of specialty in dealing with agricultural products causes fall of value of products, showing the limit to lose price-competitiveness. Especially, because lack of specialty in distribution and circulation such as storage and wrapping does not solve limit factors in distance, the distribution and circulation has been limited to a form of import and export within short-distant region. Therefore, need for distribution out-sourcing which can satisfy specialty in managing distribution and circulation and it is needed to establish more effective distribution system. Second, among tangible and intangible services which promote the efficiency of the whole distribution, a function building distribution environment which includes distribution information, system for standard and inspection, distribution finance, system for diversification of risks, education and training, distribution administration and tax system is wanted. In general, such a function building distribution environment is difficult to be changed and supplement innovatively because its effect compared with investment does not appear immediately despite of its necessity. Especially, in case of distribution of agricultural products, as a function of collecting and distributing is performed individually through various channels, the importance of distribution information and standardization is getting more focus due to the problem of repetition of work and lack of specialty. Also, efficient management of distribution is quite difficult due to lack of professionals in distribution, so support to professional education is needed. Third, though effort to keep self-sufficiency ratio of staple food, rice is regarded as important at the government level, level of dependency on overseas of others crops is high. Therefore, plan for stable securing food resources aside from staple food is also necessary. Especially, governmental organizations of agricultural products distribution in Korea are production-centered and have unreasonable structure whose function at the aspect of distribution and consumption is quite insufficient. And development of new distribution channels which can deal with changes in distribution environment and they do not achieve actual results of strategy for distribution due to non-positive strategy for price distribution. That is, it implies the possibility that base for supply will become vulnerable because it does not mediate appropriate interests on total distribution channels such as manufacturers, wholesale dealers and vendors by emphasizing consumer protection excessively in the distribution of agricultural products. Therefore, this study examined fundamental concept and actual situation for our investment to overseas agriculture, drew necessities, considerations, problems, etc. of overseas agricultural investment and suggested improvements at the level of distribution for price competitiveness of agricultural products cultivated in overseas under five aspects; government's indirect support, distribution's modernization and distribution information function's strengthening, government's political support for distribution facility, transportation route, load and unloading works' improvement, price competitiveness' securing, professional manpower's cultivation by education and training, etc. Here are some suggestions for foreign produce importation. First, the government should conduct a survey on the current distribution channels and analyze the situation to establish a measure for long-term development plans. By providing each agricultural area with a guideline for planning appropriate production of crops, the government can help farmers be ready for importation, and prevent them from producing same crops all at the same time. Government can sign an MOU with the foreign government and promote the importation so that the development of agricultural resources can be stable and steady. Second, the government can establish a strategy for an effective distribution system by providing farmers and agriculture-related workers with the distribution information such as price, production, demand, market structure and location, feature of each crop, and etc. In order for such distribution system to become feasible, the government needs to reconstruct the current distribution system, designate a public organization for providing distribution information and set the criteria for level of produce quality, trade units, and package units. Third, the government should provide financial support and a policy to seek an efficient distribution channel for foreign produce to be delivered fresh: the government should expand distribution facilities (for selecting, packaging, storing, and processing) and transportation vehicles while modernizing old facilities. There should be another policy to improve the efficiency of unloading, and to lower the cost of distribution. Fourth, it is necessary to enact a new law covering exceptional cases for importing produce in order to maintain the price competitiveness; currently the high tariffs is keeping the imported produce from being distributed domestically. However, the new adjustment should be made carefully within the WTO regulations since it can create a problem from giving preferential tariffs. The government can also simplify the distribution channels in order to reduce the cost in the distribution process. Fifth, the government should educate distributors to raise the efficiency and to modernize the distribution system. It is necessary to develop human resources by educating people regarding the foreign agricultural environment, the produce quality, management skills, and by introducing some successful cases in advanced countries.

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The Influence of Organizational Commitment, Job Commitment and Job Satisfaction on Professionalism Perceived by Radiotechnologists Working in the Department of Radiation Oncology (방사선종양학과에 근무하는 방사선사의 조직몰입, 직무몰입, 직무만족이 전문 직업성에 미치는 영향)

  • Gim, Yang-Soo;Lee, Sun-Young;Lee, Joon-Seong;Gwak, Geun-Tak;Pak, Ju-Gyeong;Lee, Seung-Hoon;Hwang, Ho-In;Cha, Seok-Yong
    • The Journal of Korean Society for Radiation Therapy
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    • v.24 no.2
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    • pp.67-75
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    • 2012
  • Purpose: The study is to check the specialty of radiotherapists working in the department of radiation oncology and find job satisfaction, organizational commitment and job commitment having an effect on professional parts. After making analysis of the mutual relation, it is to provide radiotechnologists with making progress in the future. Materials and Methods: From March 2 to March 30, we had carried out a survey with email. It is possible to have 272 questionnaires answered in the survey. We make use of SPSS 13.0 for Windows to analyze the data collected for study. Frequency and a percentage are meant to show general characteristics, and t-test and ANOVA to do the difference between general properties and professionalism. Pearson's correlation coefficient also is meant to do the correlation of professionalism, organizational job commitment and job satisfaction, and multiple regression analysis to do the factor for a relevant variable to affect professionalism. Results: There are subdivisions in the professionalism informing us of the self-regulation $17.74{\pm}2.32/3.55{\pm}.46$, a sense of calling $17.58{\pm}2.63/3.52{\pm}.53$, reference of the professional $17.14{\pm}2.39/3.43{\pm}.48$, service to the public $15.97{\pm}2.48/3.19{\pm}50$, and autonomy $15.68{\pm}2.28/3.14{\pm}46$. Grand mean turns out to be $83.89{\pm}7.63$(Summation of items)/$3.37{\pm}0.49$ (Numbers of items). When it comes to a statistical relation between general characteristics and professionalism, the statistics have it that these come within age (P<.001), period of employment (P<.001), education status (P<.05), a monthly income (P<.001), radiotherapists who get a special license (P<.001), the position (P<.001), and an opportunity for developing (P<.001). As a result of organizational commitment, job commitment, and job satisfaction, grand mean in organizational commitment proves to be $80.10{\pm}8.15/3.34{\pm}.34$. There are subvisions showing affective commitment $28.64{\pm}4.61$/3.58, continuance commitment $27.54{\pm}4.22/3.44{\pm}.53$, and normative commitment $23.95{\pm}2.94/2.99{\pm}.37$ in order of precedence. The average grade in job commitment is $32.47{\pm}5.77/3.30{\pm}.60$ and that in job satisfaction is $63.39{\pm}10.16/3.17{\pm}.51$, respectively. We find the positive relationship between professionalism and organizational commitment (r=.522, P<.05), between professionalism and job commitment (r=.444, P<.05), and between professionalism and job satisfaction (r=.507, P<.05). And we also get the positive relationship between organizational commitment and job commitment (r=.549, P<.05), between organizational commitment and job satisfaction (r=.433, P<.05), and between job commitment and job satisfaction (r=.462, P<.05). To catch the factors influencing the professionalism of radiotherapists, we used multiple regression analysis. According to the final model, it appears affective commitment (B=.755, P<.05), normative commitment (B=.305, P<.05), job satisfaction (B=.092, P<.05), an opportunity for developing (B=-1.505, P<.05), and the position (B=-1.155, P<.05) in order of precedence. It seems that explaining influece on $R^2$ is 0.504. Conclusion: The results of the factors that influence professionalism working as radiotherapists in the department of radiation oncology have it that the more affective commitment, normative commitment, and job satisfaction we feel, the more professionalism we recognize. We think that the focus of professionalism is increased if getting the chances for radiotherapists to have little to do with developing opportunities given.

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