Purpose: electrophilic $^{18}F(T_{1/2}=110\;min)$ radionuclide in the form of $[^{18}F]F_2$ gas is of great significance for labeling radiopharmaceuticals for positron omission tomography (PET). However, its production In high yield and with high specific radioactivity is still a challenge to overcome several problems on targetry. The aim of the present study was to develop a method suitable for the routine production of $[^{18}F]F_2$ for the electrophilic substitution reaction. Materials and Methods: The target was designed water-cooled aluminum target chamber system with a conical bore shape. Production of the elemental fluorine was carried out via the $^{18}O(p,n)^{18}F$ reaction using a two-step irradiation protocol. In the first irradiation, the target filled with highly enriched $^{18}O_2$ was irradiated with protons for $^{18}F$ production, which were adsorbed on the inner surface of target body. In the second irradiation, the mixed gas ($1%[^{19}F]F_2/Ar$) was leaded into the target chamber, fellowing a short irradiation of proton for isotopic exchange between the carrier-fluorine and the radiofluorine absorbed in the target chamber. Optimization of production was performed as the function of irradiation time, the beam current and $^{18}O_2$ loading pressure. Results: Production runs was performed under the following optimum conditions: The 1st irradiation for the nuclear reaction (15.0 bar of 97% enriched $^{18}O_2$, 13.2 MeV protons, 30 ${\mu}A$, 60-90 min irradiation), the recovery of enriched oxygen via cryogenic pumping; The 2nd irradiation for the recovery of absorbed radiofluorine (12.0 bar of 1% $[^{19}F]fluorine/argon$ gas, 13.2 MeV protons, 30 ${\mu}A$, 20-30 min irradiation) the recovery of $[^{18}F]fluorine$ for synthesis. The yield of $[^{18}F]fluorine$ at EOB (end of bombardment) was achieved around $34{\pm}6.0$ GBq (n>10). Conclusion: The production of $^{18}F$ electrophilic agent via $^{18}O(p,n)^{18}F$ reaction was much under investigation. Especially, an aluminum gas target was very advantageous for routine production of $[^{18}F]fluorine$. These results suggest the possibility to use $[^{18}F]F_2$ gas as a electrophilic substitution agent.
Purpose: To localize and compare the neural basis of verbal and visual human working memory, we performed functional activation study using $H_2^{15}O$ PET. Materials and Methods: Repeated $H_2^{15}O$ PET scans with one control and three different activation tasks were performed on six right-handed normal volunteers. Each activation task was composed of 13 match-ing trials. On each trial, four targets, a fixation dot and a probe were presented sequentially and subject's task was to press a response button to indicate whether or not the probe was one of the previous targets. Short meaningful Korean words, simple drawings and monochromic pictures of human faces were used as matching objects for verbal or visual memory. All the images were spatially normalized and the differences between control and activation states were statistically analyzed using SPM96. Results: Statistical analysis of verbal memory activation with short words showed activation in the left Broca's area, promoter cortex, cerebellum and right cingulate gyrus. In verbal memory with simple drawings, activation was shown in the larger regions including where activated with short words and left superior temporal cortex, basal ganglia, thalamus, prefrontal cortex, anterior portion of right superior temporal gyrus and right infero-lateral frontal cortex. On the other hand, the visual memory task activated predominantly right-sided structures, especially inferior frontal cortex, supplementary motor cortex and superior parietal cortex. Conclusion: The results are consistent with the hypothesis of the laterality and dissociation of the verbal and visual working memory from the invasive electrophysiological studies and emphasize the pivotal role of frontal cortex and cingulate gyrus in working memory system.
Purpose: Simple X-ray study and bone scan have limitations for early diagnosis of bone or bone marrow lesions in multiple myeloma. The purpose of this study was to evaluate the diagnostic usefulness of bone marrow immunoscintigraphy using anti-granulocyte monoclonal antibody for the evaluation of bone involvement in multiple myeloma. Materials and Methods: In 22 patients (Male: 15, Female: 7) with multiple myeloma, we performed whole-body immunoscintigraphy using $^{99m}Tc$-labelled antigranulocyte antibody (BW 250/183, Scintimum $Granulozyt^{(R)}$ CIS, France) and compared the findings with those of simple bone radiography and $^{99m}Tc$-MDP bone scan. Abnormal findings in bone marrow scintigraphy were, considered to be present in case of expansion of peripheral bone marrow or focal photon defect in axial bones. Results: Marrow expansion was noted in 15 of 22 patients (68%). Focal photon defects were found in 18 patients (82%). While one (33%) of 3 patients with Stage II disease showed focal defects in bone marrow scan, abnormal focal defects were observed in 17 of 19 (90%) patients with Stage III. Among 124 focal abnormal sites which were observed in bone marrow scan, bone scan or simple bone radiography, bone marrow scan detected 92 sites (74%), whereas 82 sites (66%) were observed in simple bone radiography(58 sites, 47%) or bone scan(40 sites, 32%). Fifty-one (41%) out of 124 bone lesions were detected by bone marrow scan only, and located mostly in thoracolumbar spine. Conclusion: Bone marrow scan using $^{99m}Tc$-labelled antigranulocyte antibody seems to be a more sensitive procedure for the detection of pathologic bone lesions than simple bone X-ray or bone scan in patients with multiple myeloma.
Purpose: Cellular uptakes of $^{99m}Tc-sestamibi(MIBI)\;and\;\;^{99m}Tc-tetrofosmin$ into cancer cell lines expressing multidrug resistance(MDR) were investigated and compared. The effects of verapamil and cyclosporin A, well-known multidrug resistant reversing agents, on cellular uptakes of both tracers were also compared. Materials and Methods: Doxorubicin-resistant HCT15/CL02 human colorectal cell and doxorubicin-resistant K562(Adr) and vincristine-resistant K562(Vcr) human leukemic cells were studied. RT-PCR analysis was used for the detection of mdr1 mRNA expression. MDR-reversal effects with verapamil and cyclosporine A were evaluated at different drug concentrations after incubation with MIBI and tetrofosmin for 1, 15, 30, 45 and 60 min, using single-cell suspensions at $1{\times}10^6cells/ml$ incubated at $37^{\circ}C$. Radioactivity in supernatants and pellets were measured with gamma well counter. Results: The cellular uptakes of MIBI and tetrofosmin in K562(Adr) and K562(Vcr) were lower than those of parental K562 cell. In HCT15/CL02 cells and K562(Adr) cells, there were no significant difference in cellular uptakes of both tracers, but cellular uptake of MIBI was higher than that of tetrofosmin in K562(Vcr) cells. Coincubation with verapamil resulted in a increase In cellular uptakes of MIBI and tetrofosmin. Verapamil increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 11.9- and 6.8-fold, by K562(Adr) cell by 14.3- and 8-fold and by K562(Vcr) cell by 7- and 5.7-fold in maximum, respectively. Cyciosporin A increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 10- and 2.4-fold, by K562(Adr) cell by 44- and 13-fold and by K562(Vcr) cell by 18.8- and 11.8-fold in maximum, respectively Conclusion: Taking together, MIBI and tetrofosmin are considered as suitable radiopharmaceuticals for defecting multidrug resistance. However, MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators. Since cellular uptakes of both tracers might differ in different cell types, further experiments regarding differences in cellular uptakes between cell types should be explored.
Purpose: ((R)-1-(2-chlorophenyl)-N-1-[$^{11}$C]methyl-N(1-propyl)-3-isoquinoline carboxamide ((R)-PK11195) is a specific ligand for the peripheral type benzodiazepine receptor and a marker of activated microglia, used to measure inflammation in neurologic disorders. We report here that a direct and simple radiosynthesis of [$^{11}$C](R)-PK11195 in mild condition using NaH suspension in DMF and one-step loop method. Materials and Methods: (R)-N-Desmethyl-PK11195 (1 mg) in DMSO (0.1 mL) and NaH suspension in DMF (0.1 mL) were injected into a semi-prep HPLC loop. [$^{11}$C]methyl iodide was passed through HPLC loop at room temperature. Purification was performed using semi-preparative HPLC. Aliquots eluted at 11.3 min were collected and analyzed by analytical HPLC and mass spectrometer. Results: The labeling efficiency of [$^{11}$C](R)-PK11195 was 71.8$\pm$8.5%. The specific activity was 11.8:$\pm$6.4 GBq/$\mu$mol and radiochemical purity was higher than 99.2%. The mass spectrum of the product eluted at 11.3 min showed m/z peaks at 353.1 (M+1), indicating the mass and structure of (R)-PK11195. Conclusion: By the one-step loop method with the [$^{11}$C]CH3l automated synthesis module, [$^{11}C$](R)-PK11195 could be easily prepared in high radiochemical yield using NaH suspension in DMF.
Non-invasive evaluation of liver function in animal models remains a challenge. Hepatoscintigraphy provides information about changes in liver size and shape, and enables to understand general liver function. Futhermore it is readily used to diagnosis complications of liver transplantation like hepatitis, rejections and biliary complications. In this study, we investigated the usefulness of evaluating the liver function in miniature pigs with $^{99m}Tc-Tin$ colloid and $^{99m}Tc-DISIDA$ which are the most commonly used radiopharmaceuticals in human medicine. In result, $^{99m}Tc-Tin$ colloid was uptaked in lung, liver, gastric wall and kidney in miniature pigs. And $^{99m}Tc-DISIDA$ showed continuous uptake images of heart, lung, liver, gallbladder and duodenum, and it was similar to human's. Therefore we could conclude $^{99m}Tc-Tin$ colloid would not be suitable for evaluating hepatic function because of it's nonspecific affinity, however $^{99m}Tc-DISIDA$ scintigraphy would be an effective method for detecting hepatobiliary function in miniature pigs.
The Basic Environmental Policy Act (BEPA) (Law No. 4257 effective 1. August 1990) sets forth the basic policies and administrative framework for environmental preservation, leaving more detailed regulations, and emission controls to separate laws targeting air, water, and solid waste, etc. The BEPA Article 31 adopts an unprecedented strict liability standard for damages as an absolute liability. The BEPA Article 31 provides for liability as follows. If a company is alleged to have caused damage through pollution of the environment, it will be liable for damages unless it can show that the pollution did not cause damages, or that it did not actually cause pollution. If the company did cause pollution, and if the pollution is the cause for the damages in question, the company will be liable irrespective of whether it was negligent or otherwise at fault. If there are two or more companies involved in the pollution, but it is unclear which company caused the damages, all of the companies will be jointly and severally liable for the damages. In this paper, the author attempts to uncover the problems of BEPA Article 31 and then seeks desirable amendments by comparing it to the German Environmental Liability Act. First, it will be necessary to provide definitions of 'companies etc.'. Second, it will be necessary to enumerate the kinds of company facilities. Third, it will be necessary to provide exclusionary clauses on material damages. Fourth, it will be necessary to show 'presumption of cause and effect'. Fifth, it will be necessary to provide a clause on 'right to information'. Sixth, it will be necessary to provide a clause for force majeure. Seventh, it will be necessary to take measures to secure abundant liability for damages which can be caused by the owner of the facility, the potential polluter. Finally, it is appropriate that Korea now legislate an Environmental Liability Act akin to the German Environmental Liability Act.
Using the 2-D and 3-D Hoffman brain phantom, 3-D Jaszczak phantom and Single Photon Emission Computed Tomography, the effects of data acquisition parameter, attenuation, noise, scatter and reconstruction algorithm on image quantitation as well as image quality were studied. For the data acquisition parameters, the images were acquired by changing the increment angle of rotation and the radius. The less increment angle of rotation resulted in superior image quality. Smaller radius from the center of rotation gave better image quality, since the resolution degraded as increasing the distance from detector to object increased. Using the flood data in Jaszczak phantom, the optimal attenuation coefficients were derived as 0.12cm$\^$-1/ for all collimators. Consequently, the all images were corrected for attenuation using the derived attenuation coefficients. It showed concave line profile without attenuation correction and flat line profile with attenuation correction in flood data obtained with jaszczak phantom. And the attenuation correction improved both image qulity and image quantitation. To study the effects of noise, the images were acquired for 1min, 2min, 5min, 10min, and 20min. The 20min image showed much better noise characteristics than 1min image indicating that increasing the counting time reduces the noise characteristics which follow the Poisson distribution. The images were also acquired using dual-energy windows, one for main photopeak and another one for scatter peak. The images were then compared with and without scatter correction. Scatter correction improved image quality so that the cold sphere and bar pattern in Jaszczak phantom were clearly visualized. Scatter correction was also applied to 3-D Hoffman brain phantom and resulted in better image quality. In conclusion, the SPECT images were significantly affected by the factors of data acquisition parameter, attenuation, noise, scatter, and reconstruction algorithm and these factors must be optimized or corrected to obtain the useful SPECT data in clinical applications.
Biological weapon is manipulated and produced from microorganisms such as bacteria, virus, rickettsia, fungi etc. It is classified as one of the Weapons of Mass Destruction (WMD) along with chemical weapon and radiological weapon. Biological weapon has a number of operational advantages over the other WMDs including ease of development and production, low cost and possibility of covert dissemination. In this study we analyze the history of biological weapon's development and the existing biological threats. Then, we predict the social impact of biological attack based on the physical properties of biological agent and infection mechanisms. By analyzing the recognition, dispersion pattern of agents, characteristics of the diseases in the biological weapon related historical events such as Sverdlovsk anthrax accident, 2001 anthrax attack, we found out some of the facts that biological attack would not likely to be recognized rapidly, produce large number of the exposed, increase number of paients who suffed from severe respiratory illness. It would lead the public health and medical service providers to be struggled with hugh burden. Base on the facts that we found from this case study, we suggested the main capabilities of public health required to respond to bioterrorism event efficiently. Syndromic surveillance and other reporting system need to be operated effeciently so that any suspicious event should be detected promptly. the pathogen which suspected to be used should be identified through laboratory diagnostic system. It is critical for the public health agency to define potentially exposed population under close cooperation with law enforcement agencies. Lastly, massive prophylaxis should be provided rapidly to the people at need by operating human and material resources effeciently. If those capacities of public health are consistantly fortified we would be able to deal with threat of bioterrorism successfully.
Purpose: Neuroreceptor PET studies require 60-120 minutes to complete and head motion of the subject during the PET scan increases the uncertainty in measured activity. In this study, we investigated the effects of the data-driven head mutton correction on the evaluation of endogenous dopamine release (DAR) in the striatum during the motor task which might have caused significant head motion artifact. Materials and Methods: $[^{11}C]raclopride$ PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (pre-task: 30-50 min, task: 70-90 min, post-task: 110-120 min) were realigned to the first frame in pre-task condition. Intra-condition registrations between the frames were performed, and average image for each condition was created and registered to the pre-task image (inter-condition registration). Pre-task PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the others. Volumes of interest (VOI) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DAR was calculated as the percent change of BP during and after the task. SPM analyses on the BP parametric images were also performed to explore the regional difference in the effects of head motion on BP and DAR estimation. Results: Changes in position and orientation of the striatum during the PET scans were observed before the head motion correction. BP values at pre-task condition were not changed significantly after the intra-condition registration. However, the BP values during and after the task and DAR were significantly changed after the correction. SPM analysis also showed that the extent and significance of the BP differences were significantly changed by the head motion correction and such changes were prominent in periphery of the striatum. Conclusion: The results suggest that misalignment of MRI-based VOI and the striatum in PET images and incorrect DAR estimation due to the head motion during the PET activation study were significant, but could be remedied by the data-driven head motion correction.
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