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Effect of $Al^{3+}$ on Labeling Efficiency and Biodistribution of $^{99m}Tc$-MDP ($Al^{3+}$ 존재가 $^{99m}Tc$-MDP의 표지효율과 생체내 분포에 미치는 영향)

  • Chang, Young-Soo;Jeong, Jae-Min;Kim, Young-Ju;Kwark, Cheol-Eun;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul;Koh, Chang-Soon
    • The Korean Journal of Nuclear Medicine
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    • v.30 no.3
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    • pp.361-366
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    • 1996
  • This study was to determine the effect of $Al^{3+}$ in $^{99m}Tc$ eluate from $^{99}Mo-^{99m}Tc$ generator on labeling efficiency and biodistribution of $^{99m}Tc$-MDP. The chromatographic analysis of $^{99m}Tc$-MDP preparations containing $Al^{3+}(0-62.5{\mu}g/ml)$ showed decreased labeling efficiency $^{99m}Tc$ pertechnetate and hydrolyzed reduced $^{99m}Tc$ fraction increased with increasing concentrations of aluminum. However, the chromatography system could not discern between hydrolyzed reduced $^{99m}Tc$ and $^{99m}Tc$ labeled colloid. $^{99m}Tc$-MDP preparations containing aluminum were relatively stable. Chromatographic analysis also confirmed that no significant differences were observed in the radiochemical purity of the filtered and the unfiltered $^{99m}Tc$-MDP preparations containing aluminum by $0.22{\mu}m$ syringe filter. In biodistribution data of ICR-mice, blood and heart uptake were increasing with increasing concentrations of aluminum, because of decreasing labeling efficiency of $^{99m}Tc$-MDP and increasing of $^{99m}Tc$ pertechnetate. However, liver and bone uptake were not significantly increased. In rat images no difference were observed at $5{\mu}g/ml\;Al^{3+}$ compare with at $0{\mu}g/ml\;Al^{3+}$, but at $10{\mu}g/ml\;Al^{3+}$ lumbar uptake was increased. As a practical conclusion, a concentration below $10{\mu}g/ml\;Al^{3+}$($10{\mu}g/ml\;Al^{3+}$ is the maximum allowed in pertechnetate eluate from $^{99}Mo-^{99m}Tc$ generator by USP.) in $^{99m}Tc$-MDP radiopharmaceutical result in low labeling efficiency. Radiochemical purity 90% of $^{99m}Tc$-MDP is the minimum allowed by USP. Therefore, when soft tissue uptake is observed in $^{99m}Tc$-MDP bone scan and labeling efficiency is above 90%, we can expect that $Al^{3+}$ in pertechnetated eluate is not the cause of soft tissue uptake.

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Expression and Clinical Significance of mTOR in Surgically Resected Non-small Cell Lung Cancer Tissues: a Case Control Study

  • Liu, Zhe;Wang, Liang;Zhang, Li-Na;Wang, Yue;Yue, Wen-Tao;Li, Qi
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6139-6144
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    • 2012
  • Aims: Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs. Methods: Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study. mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed. Results: The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent. Conclusions: Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment.

Adjuvant Radiotherapy after Breast Conserving Treatment for Breast Cancer:A Dosimetric Comparison between Volumetric Modulated Arc Therapy and Intensity Modulated Radiotherapy

  • Liu, Zhe-Ming;Ge, Xiao-Lin;Chen, Jia-Yan;Wang, Pei-Pei;Zhang, Chi;Yang, Xi;Zhu, Hong-Cheng;Liu, Jia;Qin, Qin;Xu, Li-Ping;Lu, Jing;Zhan, Liang-Liang;Cheng, Hong-Yan;Sun, Xin-Chen
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3257-3265
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    • 2015
  • Background: Radiotherapy is an important treatment of choice for breast cancer patients after breast-conserving surgery, and we compare the feasibility of using dual arc volumetric modulated arc therapy (VMAT2), single arc volumetric modulated arc therapy (VMAT1) and Multi-beam Intensity Modulated Radiotherapy (M-IMRT) on patients after breast-conserving surgery. Materials and Methods: Thirty patients with breast cancer (half right-sided and half left-sided) treated by conservative lumpectomy and requiring whole breast radiotherapy with tumor bed boost were planned with three different radiotherapy techniques: 1) VMAT1; 2) VMAT2; 3) M-IMRT. The distributions for the planning target volume (PTV) and organs at risk (OARs) were compared. Dosimetries for all the techniques were compared. Results: All three techniques satisfied the dose constraint well. VMAT2 showed no obvious difference in the homogeneity index (HI) and conformity index (CI) of the PTV with respect to M-IMRT and VMAT1. VMAT2 clearly improved the treatment efficiency and can also decrease the mean dose and V5Gy of the contralateral lung. The mean dose and maximum dose of the spinal cord and contralateral breast were lower for VMAT2 than the other two techniques. The very low dose distribution (V1Gy) of the contralateral breast also showed great reduction in VMAT2 compared with the other two techniques. For the ipsilateral lung of right-sided breast cancer, the mean dose was decreased significantly in VMAT2 compared with VMAT1 and M-IMRT. The V20Gy and V30Gy of the ipsilateral lung of the left-sided breast cancer for VMAT2 showed obvious reduction compared with the other two techniques. The heart statistics of VMAT2 also decreased considerably compared to VMAT1 and M-IMRT. Conclusions: Compared to the other two techniques, the dual arc volumetric modulated arc therapy technique reduced radiation dose exposure to the organs at risk and maintained a reasonable target dose distribution.

Synthesis Characterization and Biodistribution of $^{99m}Tc$-Ethyl-3-Isocyanobutyrate as a New Myocardial Perfusion Agent (새로운 심관관류 영상 화합물로서 $^{99m}Tc$-Ethyl-3-Isocyano-butyrate의 합성, 표지 및 체내동태에 대한 연구)

  • Lee, Myung-Chul;Cho, Jung-Hyuck;Lee, Dong-Soo;Lim, Sang-Moo;Oh, Seung-Joon;Chung, Soo-Wook;Lee, Kyung-Han;Jeong, Jae-Min;Chung, June-Key;Koh, Chang-Soon
    • The Korean Journal of Nuclear Medicine
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    • v.27 no.2
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    • pp.223-232
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    • 1993
  • Technetium labeled isonitrile analogues are widely used as myocardial perfusion imaging agents. We synthesized and characterized a new isonitrile compound, ethyl 3-isocyanobutyrate(EIB). Proton and $^{13}C$ NMR spectroscopy and thin layer chromatography with a $C_{18}$ coat was performed. EIB was easily labeled with $^{99m}TcO_4^-$- with sodium dithionite. The labeling efficiency measured by RP-HPLC was over 95%. The labeled product was stable with dilution in normal saline and with prolonged incubation at room temperature. There was no formation of secondary products or free $^{99m}TcO_4^-$. In vivo kinetics study of $^{99m}Tc$ (I) labeled EIB in rabbits showed adequate myocardial uptake, good contrast against lung background, and relatively rapid liver clearance. The heart to lung ratio was over 2.5 and the heart to liver ratio was approximately from 0.4 to 5 at 60 minutes post injection. Hepatic clearance of $^{99m}Tc-MIBI$ was faster ($t_{1/2}$=6 minutes) than that of $^{99m}Tc-MIBI$. In vivo kinetics observed in dog was similar to that in rabbit but there was faster gallbladder filling, and thus lower liver background. SPECT imaging of the canine myocardium showed favorable imaging characteristics. However, biodistribution in mice demonstrated a myocardial % injected dose/organ of less than 0.1%. This was thought to be due to interspecies difference in plasma esterase activity. In human plasma, $^{99m}Tc$ ( I ) labeled EIB was stable for at least 2 hours, without production of secondary products by HPLC. We conclude that ethyl 3-isocyanobutyrate may be a potential new myocardial perfusion imaging agent and deserves further investigation as to its usefulness for clinical use.

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Experience of Combined Liquid Based Cervical Cytology and High-Risk HPV mRNA for Cervical Cancer Screening in Thammasat University Hospital

  • Muangto, Teerapat;Chanthasenanont, Athita;Lertvutivivat, Supapen;Nanthakomon, Tongta;Pongrojpaw, Densak;Bhamarapravatana, Kornkarn;Suwannarurk, Komsun
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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    • pp.4409-4413
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    • 2016
  • Background: Cervical cancer is the second most common of malignancy found in Thai women. Human papillomavirus (HPV) infection is a major cause. The objective of the present study was to evaluate the prevalence of HPV infection and association with abnormal cervical cytology in Thai women. Materials and Methods: This study was conducted at the Gynecologic Clinic, Thammasat University, Pathum Thani, Thailand. A total of 2,144 cases who underwent annual cervical cancer screening by co-testing (liquid based cytology and HPV testing, DNA versus mRNA) during the priod from July 2013 to June 2016 were recruited in this study. Results: Prevalence of positive high risk (HR) HPV DNA and mRNA test were 19.7 and 8.4%, respectively with a statistically significant difference. Majority of cases of abnormal cytology in this study were atypical squamous cells of undetermined significance (ASC-US). In patients with ASC-US, positive HR HPV DNA was greater than in the mRNA group (10.1 and 4.5%, p<0.001). Nonetheless, there was no significant difference in participants with cervical intraepithelial neoplasia (CIN). HPV mRNA test had slightly lower sensitivity but higher negative predictive value (NPV) than the DNA test to detect abnormal cytology during cervical cancer screening (p<0.001). Both HPV test (DNA and mRNA) had equally efficacy to detect high grade precancerous lesion or higher (CIN 2+). Conclusions: Prevalence of HR HPV DNA and mRNA were 19.7 and 8.4 percent, respectively. NPV of HPV mRNA was higher than DNA test. Both tests had equal efficacy to detect CIN 2+ with sensitivity and specificity of 63% vs 55.7% and 83% vs 92%, respectively.

Myocardial Blood Flow Quantified by Low-Dose Dynamic CT Myocardial Perfusion Imaging Is Associated with Peak Troponin Level and Impaired Left Ventricle Function in Patients with ST-Elevated Myocardial Infarction

  • Jingwei Pan;Mingyuan Yuan;Mengmeng Yu;Yajie Gao;Chengxing Shen;Yining Wang;Bin Lu;Jiayin Zhang
    • Korean Journal of Radiology
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    • v.20 no.5
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    • pp.709-718
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    • 2019
  • Objective: To investigate the association of myocardial blood flow (MBF) quantified by dynamic computed tomography (CT) myocardial perfusion imaging (MPI) with troponin level and left ventricle (LV) function in patients with ST-segment elevated myocardial infarction (STEMI). Materials and Methods: Thirty-five STEMI patients who successfully had undergone reperfusion treatment within 1 week of their infarction were consecutively enrolled. All patients were referred for dynamic CT-MPI. Serial high-sensitivity troponin T (hs-TnT) levels and left ventricular ejection fraction (LVEF) measured by echocardiography were recorded. Twenty-six patients with 427 segments were included for analysis. Various quantitative parameters derived from dynamic CT-MPI were analyzed to determine if there was a correlation between hs-TnT levels and LVEF on admission and again at the 6-month mark. Results: The mean radiation dose for dynamic CT-MPI was 3.2 ± 1.1 mSv. Infarcted territories had significantly lower MBF (30.5 ± 7.4 mL/min/100 mL versus 73.4 ± 8.1 mL/min/100 mL, p < 0.001) and myocardial blood volume (MBV) (2.8 ± 0.9 mL/100 mL versus 4.2 ± 1.1 mL/100 mL, p = 0.044) compared with those of reference territories. MBF showed the best correlation with the level of peak hs-TnT (r = -0.682, p < 0.001), and MBV showed a moderate correlation with the level of peak hs-TnT (r = -0.437, p = 0.026); however, the other parameters did not show any significant correlation with hs-TnT levels. As for the association with LV function, only MBF was significantly correlated with LVEF at the time of admission (r = 0.469, p = 0.016) and at 6 months (r = 0.585, p = 0.001). Conclusion: MBF quantified by dynamic CT-MPI is significantly inversely correlated with the level of peak hs-TnT. In addition, patients with lower MBF tended to have impaired LV function at the time of their admission and at 6 months.

Regulation Roles of MICA and NKG2D in Human Renal Cancer Cells

  • Jia, Hong-Ying;Liu, Jun-Li;Yuan, Ming-Zhen;Zhou, Cheng-Jun;Sun, Wen-Dong;Zhao, Jing-Jie;Wang, Jue;Liu, Ling;Luan, Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3901-3905
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    • 2015
  • Objective: Our aim was to investigation the roles of MHC class I chain-related gene A(MICA) and natural killer cell group 2D(NKG2D) in human renal cancer cells. Materials and Methods: The expression of membrane MICA (mMICA) on renal cells and NKG2D on NK cells were detected by flow cytometry (FCM); the content of sMICA were detected by enzyme linked immunosorbent assay (ELISA) and the distribution of mMICA on renal tumor tissues by immunohistochemistry; the interaction between MICA and NKG2D was observed by antibody closed method. Results: Our results showed that the expression of mMICA in renal cancer tissues was significantly higher than in controls, where the soluble MICA was not expressed. Cytotoxic activity of NK cells was significantly reduced after exposure to NKG2D and MICA antibodies (P<0.05), and serum containing sMICA can obviously lower the function of NKG2D (P<0.05). Conclusions: The interaction of mMICA and NKG2D play important roles in mediation of cytotoxicity of NK cells in RCC. On the other hand, sMICA may mediate tumor immune escape through down- regulated NKG2D expression.

Reference Equations for the Six-Minute Walk Distance in Healthy Korean Adults, Aged 22-59 Years

  • Kim, Ah Lim;Kwon, Jae Choon;Park, In;Kim, Ji Na;Kim, Jong Min;Jeong, Bi Na;Yu, Sung Ken;Lee, Byung Ki;Kim, Yeon Jae
    • Tuberculosis and Respiratory Diseases
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    • v.76 no.6
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    • pp.269-275
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    • 2014
  • Background: The six-minute walk test has been widely used in people with chronic cardiopulmonary disorders as an outcome assessment with regards to therapeutic or prognostic determinants. This study was undertaken to determine the six-minute walk distance (6MWD) in a sample of healthy Koreans and to create a reference equation. We also compared the 6MWD of our cohort with previously published equations. Methods: Two hundred fifty-nine healthy subjects (95 males) aged 22-59 years performed two walking tests using a standardized protocol. 6MWD was defined as the greatest distance achieved from the two tests. The effect of anthropometrics on the 6MWD was also investigated. Results: The average 6MWD was $598.5{\pm}57.92m$, with significantly longer distances by males ($628.9{\pm}59.51m$) than females ($580.9{\pm}47.80m$) (p<0.001). Age, height, weight, and body mass index were significantly correlated with 6MWD in univariate analysis. Stepwise multiple regression showed height to be single independent predictor of 6MWD ($r^2$=0.205, p<0.001). The reference equations derived in Caucasian and North African populations tend to overestimate the distance walked by Korean subjects, while Asian equations underestimate it. Conclusion: The average 6MWD in these Korean populations was 600 m. The regression equation revealed that individual's height was the most significant predictor of distance, explaining 20.5% of the distance variance.

Metabotropic Glutamate Receptor and Anxiety (Metabotropic Glutamate 수용체와 불안)

  • Park, Young-Min;Yi, Hyeon-Lyung;Lee, Seung-Hwan
    • Anxiety and mood
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    • v.3 no.1
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    • pp.8-14
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    • 2007
  • Although treatments of anxiety symptom have been available for decades, the biological basis for anxiety disorders in humans is just beginning to emerge. Recently, there is a growing body of literature suggesting that group II metabotrpic glutamate (mGlu) receptors and group I mGlu receptors are important in the physiological and behavioral sequelae associated with stressful stimuli. Moreover, compounds selective for mGlu receptors, particularly mGlu2/3 and/or mGlu5, have proven as effective as classical anxiolytics in various animal models of anxiety without producing many of the unwanted side effects that are typical of current therapies. This article will focus on the emerging preclinical and clinical data that implicate modulation of the mGlu receptors as a potential anxiolytic strategy.

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