Small Animal PET Imaging with 124IFIAU for Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression in a Hepatoma Model / 핵의학분자영상

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-beta-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.

Imaging of Lung Metastasis Tumor Mouse Model using 18FFDG Small Animal PET and CT / 핵의학분자영상

PURPOSE: The purpose of this study is to image metastaic lung melanoma model with optimal pre-conditions for animal handling by using [18F]FDG small animal PET and clinical CT. MATERIALS AND METHODS: The pre-conditions for lung region tumor imaging were 16-22 h fasting and warming temperature at 30 degrees C. Small animal PET image was obtained at 60 min postinjection of 7.4 MBq [18F]FDG and compared pattern of [18F]FDG uptake and glucose standard uptake value (SUVG) of lung region between Ketamine/Xylazine (Ke/Xy) and Isoflurane (Iso) anesthetized group in normal mice. Metastasis tumor mouse model to lung was established by intravenous injection of B16-F10 cells in C57BL/6 mice. In lung metastasis tumor model, [18F]FDG image was obtained and fused with anatomical clinical CT image. RESULTS: Average blood glucose concentration in normal mice were 128.0+/-23.87 and 86.0+/-21.65 mg/dL in Ke/Xy group and Iso group, respectively. Ke/Xy group showed 1.5 fold higher blood glucose concentration than Iso group. Lung to Background ratio (L/B) in SUVG image was 8.6+/-0.48 and 12.1+/-0.63 in Ke/Xy group and Iso group, respectively. In tumor detection in lung region, [18F]FDG image of Iso group was better than that of Ke/Xy group, because of high L/B ratio. Metastatic tumor location in [18F]FDG small animal PET image was confirmed by fusion image using clinical CT. CONCLUSION: Tumor imaging in small animal lung region with [18F]FDG small animal PET should be considered pre-conditions which fasting, warming and an anesthesia during [18F]FDG uptake. Fused imaging with small animal PET and CT image could be useful for the detection of metastatic tumor in lung region.