• Title/Summary/Keyword: Fluoro

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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.

Injury of Neurons by Oxygen-Glucose Deprivation in Organotypic Hippocampal Slice Culture (뇌 해마조직 절편 배양에서 산소와 당 박탈에 의한 뇌신경세포 손상)

  • Chung, David Chanwook;Hong, Kyung Sik;Kang, Jihui;Chang, Young Pyo
    • Clinical and Experimental Pediatrics
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    • v.51 no.10
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    • pp.1112-1117
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    • 2008
  • Purpose : We intended to observe cell death and apoptotic changes in neurons in organotypic hippocampal slice cultures following oxygen-glucose deprivation (OGD), using propidium iodide (PI) uptake, Fluoro-Jade (FJ) staining, TUNEL staining and immunofluorescent staining for caspase-3. Methods : The hippocampus of 7-day-old rats was cut into $350{\mu}m$ slices. The slices were cultured for 10 d (date in vitro, DIV 10) and and exposed to OGD for 60 min at DIV 10. They were then incubated for reperfusion under normoxic conditions for an additional 48 h. Fluorescence of PI uptake was observed at predetermined intervals, and the cell death percentage was recorded. At 24 h following OGD, the slices were Cryo-cut into $15{\mu}m$ thicknesses, and Fluoro-Jade staining, TUNEL staining, and immunofluorescence staining for caspase-3 were performed. Results : 1) PI uptake was restricted to the pyramidal cell layer and DG in the slices after OGD. The fluorescent intensities of PI increased from 6 to 48 h during the reperfusion stage. The cell death percentage significantly increased time-dependently in CA1 and DG following OGD (P<0.05). 2) At 24 h after OGD, many FJ positive cells were detected in CA1 and DG. Some neurons had distinct nuclei and processes while others had fragmented nuclei and disrupted processes in CA1. TUNEL and immunofluorescent staining for caspase-3 showed increased expression of TUNEL labeling and caspase-3 in CA1 and DG at 24 h after OGD. Conclusion : The numerous dead cells in the slice cultures after OGD tended to display apoptotic changes mediated by the activation of caspase-3.

Kikuchi-Fujimoto disease mimicking malignant lymphoma with 2-[$^{18}F$]fluoro-2-deoxy-D-glucose PET/CT in children

  • Kim, Ji Eun;Lee, Eun Kyung;Lee, Jae Min;Bae, Soon Hwan;Choi, Kwang Hae;Lee, Young Hwan;Hah, Jeong Ok;Choi, Joon Hyuk;Kong, Eun Jung;Cho, Ihn Ho
    • Clinical and Experimental Pediatrics
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    • v.57 no.5
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    • pp.226-231
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    • 2014
  • Purpose: Kikuchi-Fujimoto disease (KFD) is a benign disease, which is characterized by a cervical lymphadenopathy with fever, and it often mimics malignant lymphoma (ML). 2-[$^{18}F$]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ($^{18}F$-FDG PET/CT) is a powerful imaging modality for the diagnosis, staging and monitoring of ML, with the limitations including the nonspecific FDG uptake in infectious or inflammatory processes. This study compared clinical manifestations and PET/CT findings between KFD and ML patients. Methods: We retrospectively reviewed the medical records of 23 patients with KFD and 33 patients with ML, diagnosed histopathologically, between January 2000 and May 2013 at the Department of Pediatrics, Yeungnam University Medical Center. Among them, we analyzed the clinical manifestations, laboratory findings and characteristics, and the amount of $^{18}F$-FDG uptake between 8 KFD and 9 ML patients who had $^{18}F$-FDG PET/CT. Results: The $^{18}F$-FDG PET/CT maximum standardized uptake values ($SUV_{max}$) ranged from 8.3 to 22.5 (mean, 12.0) in KFDs, and from 5.8 to 34.3 (mean, 15.9) in MLs. There were no significant differences in $SUV_{max}$ between KFDs and MLs. $^{18}F$-FDG PET/CT with ML patients showed hot uptakes in the extranodal organs, such as bone marrow, small bowel, thymus, kidney, orbit and pleura. However, none of the KFD cases showed extranodal uptake (P<0.001). $^{18}F$-FDG PET/CT findings of KFD with nodal involvement only were indistinguishable from those of ML. Conclusion: Patients who had extranodal involvement on PET/CT were more likely to have malignancy than KFD.

A Comparison of the Amount of Fluoride Ion Released and Remineralization Effect on the Initial Caries Lesion of the Various Fluoride Varnishes (시판중인 불소 바니쉬의 불소이온 유리량 및 초기우식병소의 재광화 효과 비교)

  • Lee, Kayoung;Lee, Sangho;Lee, Nanyoung;Jih, Myeongkwan
    • Journal of the korean academy of Pediatric Dentistry
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    • v.43 no.4
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    • pp.443-451
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    • 2016
  • Subjects of this study were : $FluoroDose^{(R)}$ (FD, Centrix Inc., USA), $Enamelast^{TM}$ (EL, Ultradent Product Inc., USA), $Clinpro^{TM}$ white varnish (CW, 3M ESPE, USA), $CavityShield^{TM}$ (CS, 3M ESPE, USA), V $varnish^{TM}$ (VV, Vericom, Korea), MI $varnish^{TM}$ (MI, GC, Japan). The amount of fluoride ion release was measured eight times during 168 hours to see change in accumulation with the course of time using a measuring instrument. And the remineralization rate was measured with Quantitative Light-induced Fluorescence (QLF). V $varnish^{TM}$ group and MI $varnish^{TM}$ group showed high remineralization rates with statistically significance while $CavityShield^{TM}$ group was the lowest rate of remineralization (p < 0.05). After that, several chosen samples were scanned through electron microscope (SEM). Demineralized enamel was observed as the number of enamel crystal was very small; enamel rods and crystals were highly protruding. Remineralized groups with fluoride varnishes show the decreasing tendency of the surface roughness compared to the demineralized enamel.

Inhibition of protoporphyrinogen oxidase activity and selectivity of new compound EK-5439 (신규 화합물 EK-5439의 선택성 및 protoporphyrinogen oxidase 저해활성)

  • Hong, K.S.;Kim, H.R.;Jeon, D.J.;Lee, B.H.;Song, J.H.;Cho, K.Y.;Hwang, I.T.
    • The Korean Journal of Pesticide Science
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    • v.8 no.2
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    • pp.79-87
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    • 2004
  • 3-Chloro-2-[4-chloro-2-fluoro-5-(5-methyl-3-phenyl-4,5-dihydroisoxazol-5-ylmethoxy)-phenyl]-4,5,6,7-tetrahy dro-2H-indazole(EK-5439) demonstrated rice selectivity and herbicidal activity on annual weeds, such as Echinochloa oryzicola, Monochoria vaginalis, Lindernia pyxidaria, Rotala indica, Aneilema keisak, Cyperus difformis, and Ludwigia prostrata at doses of 16-63 g a.i./ha. However, the application window was limited from pre-emergence to 5 days after transplanting. The control efficacy of EK-5439 on barnyardgrass was 4 times higher than that of oxadiazon. EK-5439 was excellently safe to the 16 different transplanted rice cultivars treated 2 days after transplanting. These compounds have the mechanism of action on the chlorophyll biosynthesis like protoporphyrinogen IX oxidase inhibitors.

The Usefulness of Integrated PET/CT Simulator for Non-Small Cell Lung Cancer Using the F-18 Fluoro-2-deoxyglucose (FDG) (포도당 유도체 불소화합물(FDG)을 이용한 비소세포폐암의 Integrated PET/CT 전산화 모의치료기에 대한 유용성 평가)

  • Na, Jong Eok;Suh, Jeong Nam;Kim, Jin Soo;Kim, Dae Seob;Hong, Dong Ki;Baek, Geum Mun
    • The Journal of Korean Society for Radiation Therapy
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    • v.25 no.1
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    • pp.41-47
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    • 2013
  • Purpose: To evaluate the usefulness of Integrated PET/CT and compare the gloss tumor volume (GTV) identified on CT, PET, PET/CT to that obtained from fluorodeoxyglucose (FDG). Materials and Methods: This experimental study was obtained using GE Discovery 690 (General Electric Healthcare, Milwaukee, MI, USA) PET/CT simulator with Gammex Laser System for five non-small cell lung cancer (NSCLC) patients. In order to increase the reproducibility of the patient setup, We have to fixed to patients using the Extended Wing Board. GTV delineation was painted using the EclipseTM ver.10 contouring program for CT, PET, PET/CT images. And then, We were to compare the changes in the GTV. Results: These results are drawn from 5 patients who have atelectasis or pneumonitis. Compared to CT defined GTV, PET was decreased by 10.5%, 11.8% and increased by 67.9%, 220%, 19.4%. PET/CT was decreased by 7.7%, 6.7%, 28% and increased by 232%, 24%. Conclusion: We were able to determine the usefulness of PET/CT simulator for NSCLC. PET/CT simulator in radiation therapy is useful to define the target volume and It is possible to delineate Objective and accurate target volume. It seems to be applicable to other areas in the near future.

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A Synthesis of New Fluorine-containing Phenylformamidines Possessing N-Dialkylaminosulfenyl Group and Their Insecticidal Activities (N-Dialkylaminosulfenyl 치환체를 갖는 새로운 불소 함유 Phenylformamidine 유도체의 합성과 살충활성)

  • Lee, Dong-Guk;Chung, Kun-Hoe;Ko, Young-Kwan;Ryu, Jae-Wook;Woo, Jae-Chun;Koo, Dong-Wan;Choi, Yong-Ho;Park, No-Joong;Kim, Tae-Joon;Choi, In-Young
    • The Korean Journal of Pesticide Science
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    • v.14 no.3
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    • pp.199-208
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    • 2010
  • Phenylformamidine derivatives are well known as insecticides for their specific activity against the insects. It has now been established that they show insecticidal activity as agonists on the octopamine receptor. In order to get a highly active compound we have intensively exploited fluorine substituted-aromatic formamidines possessing N-dialkylaminosulfeny group. Up to now, there are several candidates we found: N-(dialkylamino)sulfenyl-N-methyl-N'-(4-fluoro-2-methylphenyl)formamidines. The miticidal activity of Compound 29 show five-fold higher than Amitraz.

Synthesis and Evaluation of F-18 Labeled 2'-Deoxy-2'-fluoro-5-methyl-1-β-L-arabinofuranosyluracil (L-[18F]FMAU)

  • Jo, Nam-Hyun;Moon, Byung-Seok;Hong, Su-Hee;An, Gwang-Il;Choi, Tae-Hyun;Cheon, Gi-Jeong;Cho, Jung-Hyuck;Yoo, Kyung-Ho;Lee, Kyo-Chul;Oh, Chang-Hyun
    • Bulletin of the Korean Chemical Society
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    • v.28 no.12
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    • pp.2449-2453
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    • 2007
  • L-[18F]FMAU ([18F]1b) was prepared from the precursor 2-O-[(trifluoromethyl)-sulfonyl]-1,3,5-tri-Obenzoyl- α-L-ribofuranose, by coupling the radioactive fluoro-sugar with the corresponding silylated thymine in 4 steps. The final products, including the α and β anomers, were purified using reverse phase HPLC with an appropriate solvent (5% CH3CN/H2O) at a flow rate of 3.0 mL/min. The total elapsed time of synthesis was about 180-200 min from EOB. The α/β anomeric ratio of the compounds was about 1:9, and the radiochemical purity of the product (β-form) was >98% with decay-corrected yields of 25-35%. All radioactive samples were confirmed using co-injection with pure non-radioactive analogues in every step. In the cellular uptake in vitro test of herpes simplex virus-thymidine kinase (HSV1-TK) gene expressed cells, the percent uptake of injected dose (%ID) of L- and D-FMAU was 37.28 and 65.86, respectively after 240 min incubation. However, the relative uptake (MCA-TK/MCA cellular uptake ratio) of L-FMAU was higher than that of D-FMAU (%ID of L-FMAU, 0.36 and D-FMAU, 0.93 after 240 min incubation in MCA cells). This means that L-FMAU will show better specific HSV1-TK gene expressed cell uptake for selective HSV1-TK gene imaging.

Incidental Abnormal FDG Uptake in the Prostate on 18-fluoro-2-Deoxyglucose Positron Emission Tomography-Computed Tomography Scans

  • Kang, Pil Moon;Seo, Won Ik;Lee, Sun Seong;Bae, Sang Kyun;Kwak, Ho Sup;Min, Kweonsik;Kim, Wansuk;Kang, Dong Il
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8699-8703
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    • 2014
  • 18-fluoro-2-deoxyglucose positron emission tomography-computed tomography ($^{18}F$-FDG PET/CT) scans are commonly used for the staging and restaging of various malignancies, such as head and neck, breast, colorectal and gynecological cancers. However, the value of FDG PET/CT for detecting prostate cancer is unknown. The aim of this study was to evaluate the clinical value of incidental prostate $^{18}F$-FDG uptake on PET/CT scans. We reviewed $^{18}F$-FDG PET/CT scan reports from September 2009 to September 2013, and selected cases that reported focal/diffuse FDG uptake in the prostate. We analyzed the correlation between $^{18}F$-FDG PET/CT scan findings and data collected during evaluations such as serum prostate-specific antigen (PSA) levels, digital rectal examination (DRE), transrectal ultrasound (TRUS), and/or biopsy to confirm prostate cancer. Of a total of 18,393 cases, 106 (0.6%) exhibited abnormal hypermetabolism in the prostate. Additional evaluations were performed in 66 patients. Serum PSA levels were not significantly correlated with maximum standardized uptake values (SUVmax) in all patients (rho 0.483, p=0.132). Prostate biopsies were performed in 15 patients, and prostate cancer was confirmed in 11. The median serum PSA level was 4.8 (0.55-7.06) ng/mL and 127.4 (1.06-495) ng/mL in the benign and prostate cancer groups, respectively. The median SUVmax was higher in the prostate cancer group (mean 10.1, range 3.8-24.5) than in the benign group (mean 4.3, range 3.1-8.8), but the difference was not statistically significant (p=0.078). There was no significant correlation between SUVmax and serum PSA, prostatic volume, or Gleason score. $^{18}F$-FDG PET/CT scans did not reliably differentiate malignant or benign from abnormal uptake lesions in the prostate, and routine prostate biopsy was not usually recommended in patients with abnormal FDG uptake. Nevertheless, patients with incidental prostate uptake on $^{18}F$-FDG PET/CT scans should not be ignored and should be undergo further clinical evaluations, such as PSA and DRE.

Synthesis of Substrates for Gene Therapy Monitoring of HSV1-TK System (유전자 영상용 HSV1-TK 기질의 합성)

  • Choi, Tae-Hyun;Ahn, Soon-Hyuk;Choi, Chang-Woon;Lim, Sang-Moo;Awh, Ok-Doo
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.2
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    • pp.102-109
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    • 2002
  • Purpose : In gene therapy, tumor cells expressing the herpes simplex virus thymidine kinase are sensitive to prodrugs. Potential prodrugs IVDU and IVFRU were synthesized and radiolabeled with radioiodine for noninvasive imaging of herpes simplex virus type 1 gene expression. Material and Methods : 5-(2-trimethysilyl) vinyl-2'-deoxyuridine and 5-(2-trimethylsilyl)vinyl-2'-fluoro-2'-deoxyuridine, precursors of 5-(2--iodo)viny l-2'-deoxy uridine(IVDU) and 5-(2-iodo)-2'-vinyl-2'-deoxy-2'-fluororibofuranosyl uracil(IVFRU), were synthesized from reaction of trans-1-trimethylsillyl-2-tri-n-butylstannylethylene with 5-iodo-2'-deoxyuridine and 5-iodo-2'-fluoro-2'-deoxyuridine, respectively, on the condition of Pd catalyst. These precursors were separated from reaction mixture by silica gel column chromatography method. Each precursor was radioiodinated with radioiodine by mixing with ICI oxidizing agent. These radioiodinated compounds were purified with HPLC. Radiohalogen exchange has been shown to be effective for the synthesis of products with lower specific activity. Similarly, carrier-added and high specific activity products have been isolated in respectable radiochemical yields using ICI method. Results : Synthetic yield of precursors, IVDU and IVFRU were 43% and 18%, respectively. Radiochemical purity of both compunds was over 98%. Conclusion : We synthesized precursors of IVDU and IVFRU for monitoring of HSV1-tk gene expression. Radiotracers were radioiodinated with high radiolabeling yield by ICI method.