• Journal of Biomedical Engineering Research
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• v.35 no.3
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• pp.68-74
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• 2014

Recent research on mild cognitive impairment (MCI) has shown that cognitive and memory decline in this disease is accompanied by disruptive changes in the brain functional network. However, there have been no graph-theoretical studies using $^{11}C$-PIB PET data of the Alzheimer's Disease or mild cognitive impairment. In this study, we acquired $^{18}F$-FDG PET and $^{11}C$-PIB PET images of twenty-four normal aging control participants and thirty individuals with MCI from ADNI (Alzheimer's Disease Neuroimaging Initiative) database. Brain networks were constructed by thresholding binary correlation matrices using graph theoretical approaches. Both normal control and MCI group showed small-world property in $^{11}C$-PIB PET images as well as $^{18}F$-FDG PET images. $^{11}C$-PIB PET images showed significant difference between NC (normal control) and MCI over large range of sparsity values. This result will enable us to further analyze the brain using established graph-theoretical approaches for $^{11}C$-PIB PET images.

• The Korean Journal of Nuclear Medicine Technology
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• v.19 no.1
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• pp.12-16
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• 2015

Purpose Principal component analysis (PCA) is a method often used in the neuroimagre analysis as a multivariate analysis technique for describing the structure of high dimensional correlation as the structure of lower dimensional space. PCA is a statistical procedure that uses an orthogonal transformation to convert a set of observations of correlated variables into a set of values of linearly independent variables called principal components. In this study, in order to investigate the usefulness of PCA in the brain PET image analysis, we tried to analyze C[11]-PIB PET image as a representative case. Materials and Methods Nineteen subjects were included in this study (normal = 9, AD/MCI = 10). For C[11]-PIB, PET scan were acquired for 20 min starting 40 min after intravenous injection of 9.6 MBq/kg C[11]-PIB. All emission recordings were acquired with the Biograph 6 Hi-Rez (Siemens-CTI, Knoxville, TN) in three-dimensional acquisition mode. Transmission map for attenuation-correction was acquired using the CT emission scans (130 kVp, 240 mA). Standardized uptake values (SUVs) of C[11]-PIB calculated from PET/CT. In normal subjects, 3T MRI T1-weighted images were obtained to create a C[11]-PIB template. Spatial normalization and smoothing were conducted as a pre-processing for PCA using SPM8 and PCA was conducted using Matlab2012b. Results Through the PCA, we obtained linearly uncorrelated independent principal component images. Principal component images obtained through the PCA can simplify the variation of whole C[11]-PIB images into several principal components including the variation of neocortex and white matter and the variation of deep brain structure such as pons. Conclusion PCA is useful to analyze and extract the main pattern of C[11]-PIB image. PCA, as a method of multivariate analysis, might be useful for pattern recognition of neuroimages such as FDG-PET or fMRI as well as C[11]-PIB image.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.123-131
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• 2016

Increasing clinical demand for carbon-11 labeled radiopharmaceuticals has triggered technological advances in fields of radiochemistry and automated modules. Even though carbon-11 has a short half-life ($t_{1/2}=20.4min$), the consecutive second production of carbon-11 labeled radiopharmaceutical in one $^{11}C$-synthetic module should be delayed at least over 4 h to avoid the high radiation exposure. We herein aimed to produce two different carbon-11 labeled radiopharmaceuticals ([$^{11}C$]PIB and [$^{11}C$]methionine) by sharing of [$^{11}C$]methylation source in one $^{11}C$-synthetic module. The synthesis of $^{11}C$-labeling reagents ($[^{11}C]CH_3I$ or $[^{11}C]CH_3OTf$) is fully automated using the commercial TRACERlab $FX_{C-pro}$ module and is readily adaptable to $^{11}C$-labeling reactor for [$^{11}C$]PIB as well as another $^{11}C$-labeling apparatus for [$^{11}C$]methionine via the three-way valve. After completing the [$^{11}C$]PIB production, the re-synthesized $[^{11}C]CH_3I$ was passed through the three-way valve connected the polyetheretherketone (PEEK) line and loaded into the C18 Sep-Pak cartridge including the methionine precursor. The labeled product [^${11}C$]methionine was purified by a simple cartridge separation and reformulated into saline. The radiochemical yield of [$^{11}C$]PIB and [$^{11}C$]methionine were $5.3{\pm}0.6%$ and $18.7{\pm}0.8%$ (n.d.c.), respectively, with over 97% of radiochemical purity. The specific activity of [$^{11}C$]PIB was over $110GBq/{\mu}mol$. Total production time of two radiopharmaceuticals needs about 2 h from $1^{st}$ beam irradiation including quality control tests. Final [$^{11}C$]PIB and [$^{11}C$]methionine were satisfied all quality control test standards.

• The Korean Journal of Nuclear Medicine Technology
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• v.22 no.2
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• pp.67-73
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• 2018

$[^{11}C]PIB$ synthesis has been performed by a loop-methylation and HPLC purification in our lab. However, this method is time-consuming and requires complicated systems. Thus, we developed an on-cartridge method which simplified the synthetic procedure and reduced time greatly by removing HPLC purification step. We compared 6 different cartridges and evaluated the $[^{11}C]PIB$ production yields and specific activities. $[^{11}C]MeOTf$ was synthesized by using TRACERlab FXC Pro and was transferred into the cartridge by blowing with helium gas for 3 min. To remove byproducts and impurities, cartridges were washed out by 20 mL of 30% EtOH in 0.5 M $NaH_2PO_4$ solution (pH 5.1) and 10 mL of distilled water. And then, $[^{11}C]PIB$ was eluted by 5 mL of 30% EtOH in 0.5 M $NaH_2PO_4$ into the collecting vial containing 10 mL saline. Among the 6 cartridges, only tC18 environmental cartridge could remove impurities and byproducts from $[^{11}C]PIB$ completely and showed higher specific activity than traditional HPLC purification method. This method took only 8 ~ 9 min from methylation to formulation. For the tC18 environmental cartridge and conventional HPLC loop methods, the radiochemical yields were $12.3{\pm}2.2%$ and $13.9{\pm}4.4%$, respectively, and the molar activities were $420.6{\pm}20.4GBq/{\mu}mol$ (n=3) and $78.7{\pm}39.7GBq/{\mu}mol$ (n=41), respectively. We successfully developed a facile on-cartridge methylation method for $[^{11}C]PIB$ synthesis which enabled the procedure more simple and rapid, and showed higher molar radio-activity than HPLC purification method.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.6 no.2
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• pp.69-74
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• 2020

PIB is the first amyloid plaque PET image tracer reported for the first time in 2003, and is considered to be the best and is still being utilized due to its very high uptake and kinetic properties. Initially, it was synthesized by radioisotope labeling using a precursor containing a methoxy methyl protection group, but now it is synthesized using a 6-OH precursor that can be easily synthesized in one step using [¹¹C]methyl triflate. Carbon-11 has several limitations in clinical studies using PET because its half-life is as short as 20 minutes. In this study, in order to overcome the difficulty of this half-life, a rapid method using Sep-Pak was adopted instead of HPLC purification to significantly reduce the burden of the purification process and attempted synthesis. As a result, the synthesis time was shortened by more than 50%, and the yield of the final compound was higher than the previous result and showed relatively high specific radioactivity, confirming that it is a strategic method with high applicability for various precursors having primary amines.

• The Korean Journal of Nuclear Medicine Technology
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• v.16 no.2
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• pp.106-109
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• 2012

Purpose : The KOTRON-13 cyclotron was developed and installed in regional cyclotron centers to produce short-lifetime medical radioisotopes. However, this cyclotron has limited capacity to produce $^{11}C$ so far. In present study, we developed an effective $^{11}C$ target system combining with fluorine-18 target and applied to the production of various $^{11}C$ radiopharmaceuticals. Materials and Methods : To develop the optimal $^{11}C$ target system and effective its cooling system, we designed the $^{11}C$ target system by Stopping and Range of Ions in Matter (SRIM) simulation program and considered the cavity pressure during irradiation at target grid. In this investigation, we modified target materials, cavity shapes and the position of cooling system in $^{11}C$ target and then evaluated $[^{11}C]CO_2$ production at different beam currents, thickness of the target foil, oxygen content of nitrogen gas and target gas loading pressure. Also, we evaluate the production of several $^{11}C$ radiopharmaceuticals such as [$^{11}C$]PIB, [$^{11}C$]DASB, and [$^{11}C$]Clozapine. Results : $[^{11}C]CO_2$ was produced about 74 GBq for 30min irradiation at 60 ${\mu}A$ of beam current as following conditions: thickness of the target foil: 19 nm HAVAR, oxygen content of nitrogen: under 50 ppb, target gas loading pressure: 24 bar. Additionally, the cooling system was stable to produce $[^{11}C]CO_2$ at high beam current. The radiochemical yields of [$^{11}C$]PIB, [$^{11}C$]DASB, and [$^{11}C$]Clozapine showed about 26-38% with over 127 GBq/umol of specific activity. Conclusion : The carbon-11 target system in the KOTRON-13 cyclotron was successfully developed and showed stable production of $[^{11}C]CO_2$. These results showed that our $^{11}C$ target system will be compatible with other commercial system for the routine $^{11}C$ radiopharmaceuticals production in the KOTRON-13 cyclotron.

• 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.

• Journal of the Korean Society of Radiology
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• v.3 no.2
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• pp.11-16
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• 2009

Mercury Iodide as good sensitivity at radiation and has an easy peculiarity that operates at low voltage for other photoconductors(a-Se, a-Si, Ge, etc) Based on this characteristic, we studied about an efficiency of the digital x-ray detector in acccordance with the thickness of photoconductor. To solve the problem that is difficult to make a large area film using PVD(Physical Vapor Deposition)method, we used a PIB(Particle In Binder)method. To make a binder paste, we used a PVB(Polyvinylbutyral) as a binder and a DGME(Diethylene Glycol Monobutyl Ether), DGMEA(Diethylene Glycol Monobutyl Ether Acetate) as a solvent. Using this binder paste, we made a polycrystal mercury iodide film that has an each thickness. To evaluate the electrical properties of this films, we measured a darkcurrent, sensitivity and SNR(Signal to Noise Ratio). Mercury iodide film of the 200um thickness has good electrical properties as a result of the measurement. From this result there is a good chance that replace the existing a-Se(Amnorphous seleinum; a-se) with the mercury iodide.

• Journal of Plant Biotechnology
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• v.43 no.3
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• pp.317-331
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• 2016

Development of disease resistant plant is one of the important objectives in rice breeding programs because biotic stresses can adversely affect rice growth and yield losses. This study was conducted to identify lines with multiple-resistance genes to biotic stress among 173 hybrid rice breeding lines and germplasms using DNA-based markers. Our results showed that one hybrid rice line [IR98161-2-1-1-k1-3 (IR86409-3-1-1-1-1-1/IRBB66)] possessed 5 bacterial blight resistance genes (Xa4, xa5, Xa7, Xa13 and Xa21) while two hybrid rice lines [IR98161-2-1-1-k1-2 (IR86409-3-1-1-1-1-1/IRBB66) and 7292s (IR75589-31-27-8-33S(S1)/IR102758B)] possessed 3 bacterial blight resistance genes (Xa4, Xa7 and Xa21, and Xa3, Xa4 and xa5). Molecular survey on rice blast disease revealed that most of these lines had two different resistant genes. Only 11 lines possessed Pib, Pi-5, and Pi-ta. In addition, we further surveyed the distribution of insect resistant genes, such as Bph1, Bph18(t), and Wbph. Three hybrid breeding lines [IR98161-2-1-1-k1-3 (IR86409-3-1-1-1-1-1/IRBB66), IR98161-2-1-1-k1-2 (IR86409-3-1-1-1-1-1/IRBB66), and 7292s (IR75589-31-27-8-33S(S1) /IR102758B)] contained all three resistance genes. Finally, we obtained four hybrid rice breeding lines and germplasms [IR98161-2-1-1-k1-2 (IR86409-3-1-1-1-1-1/IRBB66), Damm-Noeub Khmau, 7290s, and 7292s (IR75589-31-27-8-33S(S1)/IR102758B)] possessing six-gene combination. They are expected to provide higher level of multiple resistance to biotic stress. This study is important for genotyping hybrid rice with resistance to diverse diseases and pests. Results obtained in this study suggest that identification of pyramided resistance genes is very important for screening hybrid rice breeding lines and germplasms accurately for disease and pest resistance. We will expand their cultivation safely through bioassays against diseases, pests, and disaster in its main export countries.