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Small Animal PET Imaging with [$^{124}I$]FIAU for Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression in a Hepatoma Model (간암 동물 모델에서 2'-fluoro-2'-deoxy-1-${\beta}$-D-arabinofuranosyl-5-[$^{124}I$iodo-uracil ($[^{124}I]FIAU$) 소동물 PET 영상 연구)

  • Chae, Min-Jeong;Lee, Tae-Sup;Kim, June-Youp;Woo, Gwang-Sun;Jumg, Wee-Sup;Chun, Kwon-Soo;Kim, Jae-Hong;Lee, Ji-Sup;Ryu, Jin-Sook;Cheon, Gi-Jeong;Choi, Chang-Woon;Lim, Sang-Moo
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.3
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    • pp.235-245
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    • 2008
  • Purpose: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the development of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-${\beta}$-D-arabino-furanosyi-5-[$^{124/125}I$]iodo- uracil ([$I^{124/125}I$]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. Material and Methods: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [$^{125}I$]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [$^{124}I$]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. Results:, Specific accumulation of [[$^{125}I$]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [$^{125}I$]FIAU uptake was linearly correlated (R2 =0.964, p =0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [$^{125}I$]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small animal PET, [$^{124}I$]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. Conclusion: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.

Study the Analysis of Comparison with AROI and MROI Mode in Gated Cardiac Blood Pool Scan (게이트심장혈액풀 스캔에서 자동 관심영역 설정과 수동 관심영역 설정 모드의 비교 분석에 관한 고찰)

  • Kim, Jung-Yul;Kang, Chun-Koo;Kim, Yung-Jae;Park, Hoon-Hee;Kim, Jae-Sam;Lee, Chang-Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.12 no.3
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    • pp.222-228
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    • 2008
  • Purpose: The objectives of this study were to compare the left ventricle ejection fraction (LVEF) from gated cardiac blood pool scan (GCBP) for analysis auto-drawing region of interest mode (AROI) and manual-drawing region of interest mode (MROI), respectively. To evaluation the relationships between values produced by both ROI modes. Materials and Methods: Gated cardiac blood pool scan using in vivo method Tc-99m Red Blood Cell were performed for 33 patients (mean age: $53.2{\pm}13.2\;y$) with objective of chemotherapy using single head gamma camera (ADAC Laboratories, Milpitas, CA). Left ventricular ejection fraction was automatically and manually measured, respectively. Results: There was significant difference statistically between AROI and MROI ($LVEF^{AROI}$: $71.4{\pm}12.4%$ vs. $LVEF^{MROI}$: $65.8{\pm}5.9%$, p=0.003). Intra-observer agreements in AROI was higher than MROI ($\gamma^{AROI}=0.964$, Cronbach's $\alpha^{AROI}=0.986$ vs. $\gamma^{MROI}=0.793$, Cronbach's $\alpha^{MROI}=0.911$), either. Additionally, there was no significant difference statistically at best septal view (${\Delta}LVEF^{BSV}=0.7{\pm}2.3%$, p=0.233), however statistically significant difference was found at badly separated septal view (${\Delta}LVEF=10.9{\pm}11.4%$, p=0.001). Moreover, Intra-observer agreements in best septal view was higher than badly separated septal view ($\gamma^{BSV}=0.939$, Cronbach's $\alpha^{BSV}=0.978$; $\gamma=0.948$, Cronbach's $\alpha=0.981$ at AROI, $\gamma^{BSV}=0.836$, Cronbach's $\alpha^{BSV}=0.936$; $\gamma=0.748$, Cronbach's $\alpha=0.888$ at MROI). Conclusion: When best septal view was acquired, LVEF by AROI and MROI indicated not different. Comparing Intra-observer agreements with AROI and MROI, the AROI tended to show higher. Therefore, it is considered that the AROI than MROI is valuable in reproducibility and objective when ROI analysis by acquire left ventricular of best septal view.

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A Study on Modernization of International Conventions Relating to Aviation Security and Implementation of National Legislation (항공보안 관련 국제협약의 현대화와 국내입법의 이행 연구)

  • Lee, Kang-Bin
    • The Korean Journal of Air & Space Law and Policy
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    • v.30 no.2
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    • pp.201-248
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    • 2015
  • In Korea the number of unlawful interference act on board aircrafts has been increased continuously according to the growth of aviation demand, and there were 55 incidents in 2000, followed by 354 incidents in 2014, and an average of 211 incidents a year over the past five years. In 1963, a number of states adopted the Convention on Offences and Certain Other Acts Committed on Board Aircraft (the Tokyo Convention 1963) as the first worldwide international legal instrument on aviation security. The Tokyo Convention took effect in 1969 and, shortly afterward, in 1970 the Convention for the Suppression of Unlawful Seizure of Aircraft(the Hague Convention 1970) was adopted, and the Convention for the Suppression of Unlawful Acts Against the Safety of Civil Aviation(the Montreal Convention 1971) was adopted in 1971. After 9/11 incidents in 2001, to amend and supplement the Montreal Convention 1971, the Convention on the Suppression of Unlawful Acts Relating to International Civil Aviation(the Beijing Convention 2010) was adopted in 2010, and to supplement the Hague Convention 1970, the Protocol Supplementary to the Convention for the Suppression of Unlawful Seizure of Aircraft(the Beijing Protocol 2010) was adopted in 2010. Since then, in response to increased cases of unruly behavior on board aircrafts which escalated in both severity and frequency,, the Montreal Protocol which is seen as an amendment to the Convention on Offences and Certain Other Acts Committed on Board Aircraft(the Tokyo Convention 1963) was adopted in 2014. Korea ratified the Tokyo Convention 1963, the Hague Convention 1970, the Montreal Convention 1971, the Montreal Supplementary Protocol 1988, and the Convention on the Marking of Plastic Explosive 1991 which have proven to be effective. Under the Tokyo Convention ratified in 1970, Korea further enacted the Aircraft Navigation Safety Act in 1974, as well as the Aviation Safety and Security Act that replaced the Aircraft Navigation Safety Act in August 2002. Meanwhile, the title of the Aviation Safety and Security Act was changed to the Aviation Security Act in April 2014. The Aviation Security Act is essentially an implementing legislation of the Tokyo Convention and Hague Convention. Also the language of the Aviation Security Act is generally broader than the unruly and disruptive behavior in Sections 1-3 of the model legislation in ICAO Circular 288. The Aviation Security Act has reflected the considerable parts of the implementation of national legislation under the Beijing Convention and Beijing Protocol 2010, and the Montreal Protocol 2014 that are the modernized international conventions relating to aviation security. However, in future, when these international conventions would come into effect and Korea would ratify them, the national legislation that should be amended or provided newly in the Aviation Security Act are as followings : The jurisdiction, the definition of 'in flight', the immunity from the actions against the aircraft commander, etc., the compulsory delivery of the offender by the aircraft commander, etc., the strengthening of penalty on the person breaking the law, the enlargement of application to the accomplice, and the observance of international convention. Among them, particularly the Korean legislation is silent on the scope of the jurisdiction. Therefore, in order for jurisdiction to be extended to the extra-territorial cases of unruly and disruptive offences, it is desirable that either the Aviation Security Act or the general Crime Codes should be revised. In conclusion, in order to meet the intelligent and diverse aviation threats, the Korean government should review closely the contents of international conventions relating to aviation security and the current ratification status of international conventions by each state, and make effort to improve the legislation relating to aviation security and the aviation security system for the ratification of international conventions and the implementation of national legislation under international conventions.