원저 : 간암 동물 모델에서 2'-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-[124I]iodo-uracil ([124I]FIAU) 소동물 PET 영상 연구 (Small Animal PET Imaging with [124I]FIAU for Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression in a Hepatoma Model) |
Author |
채민정1,3, 이태섭2, 김준엽2, 우광선2, 정위섭2, 전권수2, 김재홍2, 이지섭2, 류진숙3, 천기정1,2, 최창운1,2, 임상무1,2, |
Min Jeong Chae, M.D.1, Tae Sup Lee, Ph.D.2, June Youp Kim, M.S2, Gwang Sun Woo, BA2, Wee Sup Jumg2, Kwon Soo Chun, Ph.D.2, Jae Hong Kim2, Ji Sup Lee2, Jin-Sook Ryu, M.D. & Ph.D.3, Gi Jeong Cheon, M.D. & Ph.D.1,2, Chang Woon Choi, M.D. & Ph.D.1,2 and Sang |
Affiliation |
원자력의학원 핵의학과1, 분자영상연구부2, 울산의과대학교 서울아산병원 핵의학과3 1Department of Nuclear Medicine and 2Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea; 3Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. |
Abstract |
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 develoopement 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-β-D-arabino-furanosyl-5-[124/125I]iodo- uracil ([124/125I]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 [125I]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [124I]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors.
Results: Specific accumulation of [125I]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. [125I]FIAU uptake was linearly correlated (R2=0.964, p=0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [125I]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 aninal PET, [124I]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. |
Keyword |
FIAU, HSV1-tk, Small animal PET, HCC |
Full text Article |
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