• 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.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.19-29
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• 1997

Recently, [I-123]IPT SPECT has been used for early diagnosis of Parkinson's patients(PP) by imaging dopamine transporters. The dynamic time activity curves in basal ganglia(BG) and occipital cortex(OCC) without blood samples were obtained for 2 hours. These data were then used to measure dopamine transporters by operationally defined ratio methods of (BG-OCC)/OCC at 2 hrs, binding potential $R_v=k_3/k_4$ using graphic method or $R_A$= (ABBG-ABOCC)/ABOCC for 2 hrs, where ABBG represents accumulated binding activity in basal ganglia(${\int}^{120min}_0$ BG(t)dt) and ABOCC represents accumulated binding activity in occipital cortex(${\int}^{120min}_0$ OCC(t)dt). The purpose of this study was to examine the IPT pharmacokinetics and investigate the usefulness of simplified methods of (BG-OCC)/OCC, $R_A$, and $R_v$ which are often assumed that these values reflect the true values of $k_3/k_4$. The rate constants $K_1,\;k_2\;k_3$ and $k_4$ to be used for simulations were derived using [I-123]IPT SPECT and aterialized blood data with a standard three compartmental model. The sensitivities and time activity curves in BG and OCC were computed by changing $K_l$ and $k_3$(only BG) for every 5min over 2 hours. The values (BG-OCC)/OCC, $R_A$, and $R_v$ were then computed from the time activity curves and the linear regression analysis was used to measure the accuracies of these methods. The late constants $K_l,\;k_2\;k_3\;k_4$ at BG and OCC were $1.26{\pm}5.41%,\;0.044{\pm}19.58%,\;0.031{\pm}24.36%,\;0.008{\pm}22.78%$ and $1.36{\pm}4.76%,\;0.170{\pm}6.89%,\;0.007{\pm}23.89%,\;0.007{\pm}45.09%$, respectively. The Sensitivities for ((${\Delta}S/S$)/(${\Delta}k_3/k_3$)) and ((${\Delta}S/S$)/(${\Delta}K_l/K_l$)) at 30min and 120min were measured as (0.19, 0.50) and (0.61, 0,23), respectively. The correlation coefficients and slopes of ((BG-OCC)/OCC, $R_A$, and $R_v$) with $k_3/k_4$ were (0.98, 1.00, 0.99) and (1.76, 0.47, 1.25), respectively. These simulation results indicate that a late [I-123]IPT SPECT image may represent the distribution of the dopamine transporters. Good correlations were shown between (3G-OCC)/OCC, $R_A$ or $R_v$ and true $k_3/k_4$, although the slopes between them were not unity. Pharmacokinetic computer simulations may be a very useful technique in studying dopamine transporter systems.

• Bulletin of the Korean Chemical Society
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• v.26 no.1
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• pp.91-96
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• 2005

O-(3-[$^{18}$F]Fluoropropyl)-L-tyrosine (L-[$^{18}$F]FPT) was synthesized by nucleophilic radiofluorination followed by acidic hydrolysis of protective groups and evaluated with 9 L tumor bearing rat. L-[$^{18}$F]FPT is an homologue of O-(2-[$^{18}$F]fluoroethyl)-L-tyrosine (L-[$^{18}$F]FET) which recently is studied as a tracer for tumor imaging using positron emission tomography (PET). [$^{18}$F]FPT was directly prepared from the precursor of O-(3-ptoluenesulfonyloxypropyl)- N-(tert-butoxycarbonyl)-L-tyrosine methyl ester. FPT-PET image was obtained at 60 min in 9 L tumor bearing rats. The radiochemical yield of [$^{18}$F]FPT was 0-45% (decay corrected) and the radiochemical purity was more than 95% after HPLC purification. The total time elapsed for the synthesis of [$^{18}$F]FPT was 100 min from EOB (End-of-bombardment). A comparison of uptake studies between [$^{18}$F]FPT and [$^{18}$F]FET was performed. In biodistribution, [$^{18}$F]FPT showed similar pattern with [$^{18}$F]FET in various tissues, but [$^{18}$F]FPT showed low uptake in brain. Furthermore, [$^{18}$F]FPT showed higher tumor-to-brain ratio than [$^{18}$F]FET. In conclusion, [$^{18}$F]FPT seems to be more useful amino acid tracer than [$^{18}$F]FET for brain tumors imaging with PET.

• The Korean Journal of Nuclear Medicine
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• v.25 no.1
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• pp.46-52
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• 1991

Radioaerosol inhalation imaging (RII) has been used in radionuclide pulmonary studies for the past 20 years. The method is well accepted for assessing regional ventilation because of its usefulness, easy fabrication and simple application system. To evaluate its clinical utility in the study of impaired regional ventilation in bronchial asthma, we obtained and analysed RIIs in 31 patients (16 women and 15 men; age ranging 21-76 years) with typical bronchial asthma at the Department of Radiology, Kangnam St. Mary's Hospital, Catholic University Medical college, from January, 1988 to August, 1989. Scintiscans were obtained with radioaerosol produced by a BARC(Bhabha Atomic Reserch Center, India) nebulizer with 15 mCi of $^{99m}Tc-phytate$. The scanning was peformed in anterior, posterior and lateral projections following 5-minute inhalation of radioaerosol on sitting position. The scans were analyzed and correlated with the results of pulmonary function study and the findings of chest radiography. Fifteen patients had concomitant lung perfusion image with $^{99m}Tc-MAA$. Follow-up scans were obtained in 5 patients after bronchodilator therapy. The patients were divided into (1) attack type (4 patients), (2) resistant type (5 patients), (3) remittent type (10 patients) and (4) bronchitic type (12 patients). Chest radiography showed hyperinflation, altered pulmonary vascularity, thickening of the bronchial wall and accentuation of basal interstitial markings in 26 of the 31 patients. Chest radiographs were norma! in the remaining 5 patients. Regardless of type, the findings of RII were basically the same, and characterized by the deposition of radioaerosol in the central parts or in the main respiratory air ways along with mottled nonsegmental ventilation defects in the periphery. Peripheral parenchymal defects were more extensive than that of expected findings from clinical symptoms, pulmonary function test and chest radiograph. Broomstick sign was present in 17 patients. The abnormality of RII was poorly correlated with perfusion scans. In all 5 patients treated with bronchodilators, follow-up study demonstrated a decrease in the degree of radioaerosol deposition in the central air way with improved ventilation defects. This study indicates that RII is a useful technique for the evaluation of regional ventilation abnormality and the effect of treatment with bronchodilators in patients with bronchial asthma.

• The Korean Journal of Nuclear Medicine
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• v.29 no.1
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• pp.15-21
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• 1995

To evaluate availability of cerebral radionuclide imaging for diagnosis of brain death, we examined 25 patients with a suspected clinical diagnosis of brain death. 8 patients were studied by $^{99m}Tc$ DTPA and 15 patients were studied by $^{99m}Tc$ HMPAO (Hexamethyl propyleneamine oxime). Seven patients with $^{99m}Tc$ DTPA studies revealed absence of cerebral blood flow and sagittal sinus activity. All of 15 patients with $^{99m}Tc$ HMPAO studies revealed complete absence of cerebral perfusion. The results of the cerebral radionuclide studies of brain death correlated with other clinical conditions, such as intracranial pressure(ICP), EEG, transcranial doppler sonography(TCDS), and neurologic examination. The ICP of 8 patients, who are confirmed by brain death with $^{99m}Tc$ HMPAO study are elevated in all cases. In conclusion, cerebral radionuclide imaging for diagnosis of brain death is available. $^{99m}Tc$ HMPAO imaging is unequivocal, easily interpreted, well reflect the physiologic state of increased ICP, and provides adequate assessment of posterior fossa activity. In addition, the SPECT imaging with $^{99m}Tc$ HMPAO produces more accurate results due to it's superiority of image contrast and proper localization of radiopharmaceutical distribution than conventional planar imaging.

• Journal of the Korean Society of Radiology
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• v.15 no.6
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• pp.849-853
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• 2021

PET images used in medical diagnoses are created using positron emitting radionuclides. The radiation used for imaging is generated at 0.511 MeV by p-annihilation. The CSDA range is the distance the particle radiation flew physically, and it is different from the range shown in PET images. This study proposes a novel method that uses radiological criteria to measure this range. The experiment was conducted by applying the MCNP6 simulation to positron emitting nuclides ¹⁸F, ¹¹C, ¹³N, and ¹⁵O. Radiological criteria were based on the location of the p-annihilation event, which is also the image signal. Results showed the radiological range of positrons to be 2.3, 3.9, 5.0, and 7.9 mm for ¹⁸F, ¹¹C, ¹³N, and ¹⁵O, respectively. The higher the positron energy, the larger its difference from the CSDA range. Positron emitting nuclide is being developed and studied as a nuclide for dosimetry or radiotherapy. Further research needs to be conducted into various positron ranges.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.468-477
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• 2009

Purpose: Hydrodynamic-based procedure is a simple and effective gene delivery method to lead a high gene expression in liver tissue. Non-invasive imaging reporter gene system has been used widely with herpes simplex virus type 1 thymidine kinase (HSV1-tk) and its various substrates. In the present study, we investigated to image the expression of HSV1-tk gene with 5-(2-iodovinyD-2'-deoxyuridine (IVDU) in mouse liver by the hydrodynamicbased procedure. Materials and Methods: HSV1-tk or enhanced green fluorescence protein (EGFP) encoded plasmid DNA was transferred into the mouse liver by hydrodynaminc injection. At 24 h post-injection, RT-PCR, biodistribution, fluorescence imaging, nuclear imaging and digital wholebody autoradiography (DWBA) were performed to confirm transferred gene expression. Results: In RT-PCR assay using mRNA from the mouse liver, specific bands of HSV1-tk and EGFP gene were observed in HSV1-tk and EGFP expressing plasmid injected mouse, respectively. Higher uptake of radiolabeled IVDU was exhibited in liver of HSV1-tk gene transferred mouse by biodistribution study. In fluorescence imaging, the liver showed specific fluorescence signal in EGFP gene transferred mouse. Gamma-camera image and DWBA results showed that radiolabeled IVDU was accumulated in the liver of HSV1-tk gene transferred mouse. Conclusion: In this study, hydrodynamic-based procedure was effective in liver-specific gene delivery and it could be quantified with molecular imaging methods. Therefore, co-expression of HSV1-tk reporter gene and target gene by hydrodynamic-based procedure is expected to be a useful method for the evaluation of the target gene expression level with radiolabeled IVDU.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.10
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• pp.4418-4424
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• 2011

This study is aimed to assess the effect of the gamma ray of 511keV energy which is emitted from phantom where the positron emission radionuclide was injected on X-ray CT image. As a scanning method, the CT number and pixel value of the reference image where water was injected(0 mCi), and those acquired by changing the capacity of 18F(Fluorine), positron emission radionuclide, into 1 mCi, 2 mCi, 5 mCi, and 10 mCi were measured. As a result of measuring the CT number(HU) of the phantom image where the positron emission radionuclide($^{18}F$) was injected, there were reference water ($-7.58{\pm}0.66$ HU), 1 mCi($-9.85{\pm}0.50$ HU), 2 mCi($-10.27{\pm}0.21$ HU), 5 mCi($-11.31{\pm}0.66$ HU), and 10 mCi($-13.47{\pm}0.38$ HU). Compared with the image where it was filled with water, there was a reduction of 5.89 Hu in 10 mCi, 3.73 in 5 mCi, 2.69 HU in 2 mCi, and 2 HU in 1 mCi. As for the pixel value of the phantom image, there were reference water ($-2.70{\pm}0.75$), 1 mCi($-4.72{\pm}0.58$), 2 mCi($-6.01{\pm}0.78$), 5 mCi($-6.10{\pm}0.84$), and 10 mCi($-8.20{\pm}0.60$). Compared with the reference image, there was a reduction of 5.50 in 10 mCi, 3.40 in 5 mCi, 3.10 in 2 mCi, and 2.02 in 1 mCi. Through this experiment, it was indicated that, with the increase in the dose of the positron emission radionuclide($^{18}F$), the CT number and the pixel value of the image reduced proportionally, and the width of reduction showed a similar value, too. Accordingly, according to the degree of change in X-ray CT image due to the positron emission radionuclide in the quality control item of PET/CT, the proper standard should be established and it should be periodically managed.

• The Korean Journal of Nuclear Medicine
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• v.35 no.5
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• pp.324-333
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• 2001

Purpose: $^{123}I$-labeled fatty acids have been used in the evaluation of regional myocardial energy metabolism. This study aimed to evaluate the usefulness of $^{123}I$-BMIPP as a liposarcoma-imaging agent. Materials and Methods: We compared in vitro uptakes between liposarcoma(SW872) and glioma(9L) cell lines, and examined biodistribution and in vivo images of $^{123}I$-BMIPP in liposarcoma-bearing nude mice. Cold-BMIPP was labeled with $^{123}I\;using\;Cu^{2+}$ as catalyst. After purification by Sep-pak, radiochemical purity was determined by TLC. We compared cellular uptake between glioma and liposarcoma after incubation of 5, 10, 15, 30, 60, 120, and 180 mins with culture medium containing $^{123}I$-BMIPP. The difference in biodistribution was determined between non-feeding (water only) group for 18 hr and feeding group in normal mice (n=6/group) at 0.5, 2, and 24 hr. In liposarcoma-hearing nude mice model, liposarcoma, SW872, ceil lines were injected subcutaneously into the felt thigh of nude mice. The biodistribution of $^{123}I$-BMIPP was evaluated at 0.5, 2, and 24 hr (n:5 / group) and in vivo Image of $^{123}I$-BMIPP was obtained with gamma camera at 2 and 24 hr in liposarcoma-hearing nude mice. Results: Radiolabeling yield and radiochemical purity were 95% and above 99%, respectively. SW872 cell line showed more increased uptake than 9L with 1.5 times at 180 mins. The clearance of $^{123}I$-BMIPP in various tissues was more delayed in the non-feeding group than in the feeding group, especially at delayed time (24 hr) in normal mice, and the major excreting organ was the gastrointestinal tract. In liposarcoma-bearing nude mice, tumor/blood ratio of $^{123}I$-BMIPP was 0.94, 0.75, and 1.38 and tumor/muscle ratio was 0.66, 1.53, and 1.11 at 0.5, 2, and 24hr, respectively. $^{123}I$-BMIPP was selectively localized in liposarcoma at 24 hr image. Conclusions: These results suggest that $^{123}I$-BMIPP can be used as a liposarcoma-imaging agent.

• Journal of radiological science and technology
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• v.36 no.3
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• pp.193-200
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• 2013

There are many concerns about radiation exposure in Korea after Fukushima Nuclear Plant Accident on 2011 in Japan. As some isotope materials are detected in Korea, people get worried about the radioactive material. In addition, the mass media create an air of anxiety that jump on the people's fear instead of scientific approach. Therefore, for curbing this flow, health, medical institute from the world provide a variety of information about medical radiation safety and hold the campaign which can give people the image that medical radiation is safe. At this, the Korean Food and Drug Administration(KFDA) suggested that make the alliance of medical radiation safety and culture on August, 2011. Seven societies and institutions related medical radiation started to research and advertise the culture of medical radiation safety in Korea. In this report, mainly introduce the activities of the Korean Alliance for Radiation Safety and Culture in Medicine(KARSM) for spreading culture of medical radiation safety from 2011 to 2012.