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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.

The Location and Landscape Composition of Yowol-pavilion Garden Interpreted from Tablet & Poetry (편액과 시문으로 본 요월정원림(邀月亭園林)의 입지 및 조영 해석)

  • Lee, Hyun-Woo;Kim, Sang-Wook;Ren, Qin-Hong
    • Journal of the Korean Institute of Traditional Landscape Architecture
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    • v.32 no.3
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    • pp.32-45
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    • 2014
  • The study attempts to interpret original location and landscape composition of Yowol-pavilion Garden under the premise that tablet and poetry are important criteria for inference of unique location and landscape composition of a pavilion garden. The study raises the meaning, status, and value of Yowol Pavilion Garden as a cultural asset. The results of the study are as follows. First, Yowol-pavilion Garden was a place where famous Confucius scholars in Joseon Dynasty in 16th Century, including Kim, Kyung-Woo, the owner of the garden, used to share the taste for the arts and poetries with their colleagues. Along with a main characteristic of Yowol Pavilion Garden as a hideout for the Confucius scholars who stayed away from a political turmoil, the new place characteristic of the garden, a bridgehead for the formation of regional identity, was discovered in the record of "Joseon-Hwanyeo-Seungram Honam-Eupji JangSeong-Eupji", As described in "The first creative poetry of Yowol-pavilion", the intention for the creation of Yowol-pavilion Garden and the motive for its landscape composition is interpreted as a space of rivalry where the world, reality and ideals are mixed up. Second, related to outstanding scenic factors and natural phenomena when taking a view from the pavilion, the name of the house 'Yowol', which means 'Greeting the moon rising on the Mt. Wolbong' is the provision of nature and taste for the arts, and is directly connected to the image of leaving the worldly. In other words, the name was identified to be the one that reflected the intention for landscape composition to follow the provision of nature separating from joy and sorrow of the mundane world. Third, as for the location, it was confirmed through "YeongGwang-Soksu-Yeoji-Seungram" that Yowol-pavilion Garden was a place where the person who made the pavilion prepared for relaxation after stepping down from a government post, and literature and various poetry show that it was also a place of outstanding scenic where Yellow-dragon River meandered facing Mt. Wolbong. Especially, according to an interview with a keeper, the visual perception frequency of the nightscape of Yowol-pavilion Garden is the highest when viewing by considering the east, the direction of Yellow-dragon River, as Suksigak[normal angle's view], towards Yowel-pavilion from the keeper's house. In addition, he said that the most beautiful landscape with high perception strength is when the moon came up from the left side of Yowol-pavilion, cuts across the Lagerstroemia india heal in front of Yowol-pavilion, and crosses the meridian between Mt. Wolbong peaks facing Yowol-pavilion. Currently, the exposure of Yowol-pavilion Garden is $SE\;141.2^{\circ}$, which is almost facing southeast. It is assumed that the exposure of Yowol-pavilion Garden was determined considering the optimized direction for appreciating the trace of the moon and the intention of securing the visibility as well as topographic conditions. Furthermore, it is presumed that the exposure of Yowol-pavilion Garden was determined so that the moon is reflected on the water of Yellow-dragon River and the moon and its reflection form a symmetry. Fourth, currently, Yowol-pavilion Garden is divided into 'inner garden sphere' composed of Yowol-pavilion, meeting place of the clan and administration building, and 'outer garden sphere' which is inclusive of entrance space, Crape Myrtle Community Garden and Pine Tree Forest in the back. Further, Yowol-pavilion Garden has been deteriorated as the edge was expanded to 'Small lake[Yong-so] and Gardens of aquatic plants sphere' and recently-created 'Yellow-dragon Pavilion and park sphere'. Fifth, at the time it was first made, Yowol-pavilion Garden was borderless gardens consisting of mountains and water taking a method of occupying a specific space of nearby nature centering around pavilion by embracing landscape viewed from the pavilion, but interpreted current complex landscapes are identified to be entirely different from landscapes of the original due to 'Different Changes', 'Fragmentation' and 'Apart piece' in many parts. Lastly, considering that Yowol-pavilion Garden belongs to the Cultural Properties Protection Zone, though not the restoration to the landscapes of the original described in tablet and literature record, at least taking a measure from the aspect of land use for minimizing adverse effect on landscape and visual damage is required.