• The Korean Journal of Nuclear Medicine
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• v.34 no.4
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• pp.294-302
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• 2000

Purpose: To investigate the mechanisms related to F-18-FDG uptake by tumors, F-18-FDG accumulation was compared with glucose transporter-1 (Glut-1) expression and hexokinase activity in various human cancer cell lines. Materials and Methods: Human colon cancer (SNU-C2A, SNU-C4, SNU-C5), hepatocellular carcinoma (SNU-387, SNU-423, SNU-449), lung cancer (NCI-H522, NCI-H358, NCI-H1299), uterine cervical cancer (HeLa, HeLa 229, HeLa S3) and brain tumor (A172, Hs 683) cell lines were used. After 24 hr incubation of $5{\times}10^5$ cells, 37 kBq F-18-FDG was added and the uptake by cells at 10 min was measured using a gamma counter. Hexokinase activity was measured by continuous spectrophotometric rate determination. To measure mitochondrial hexokinase activity, mitochondrial fraction was separated by a high speed centrifuge. Immunohistochemical staining of Glut-1 was performed, and graded as 0, 1, 2, or 3 according to expression. Results: There was difference among F-18-FDG uptake, total and mitochondrial hexokinase activity, and Glut-1 expression with different cancer cell lines. The correlations of F-18-FDG with total hexokinase and mitochondrial hexokinase activity were low (r=0.27 and 0.26, respectively). Glut-1 expression showed a good correlation with F-18-FDG uptake (p=0.81, p=0.0015). Previously, we reported no correlation of F-18-FDG uptake with hexokinase activity in colon cancer cell lines. Thus, when colon cancer cells were excluded, F-18-FDG uptake showed higher correlation with total hexokinase and mitochondrial hexokinase activity (r=0.81, p=0.0027 and r=0.81, p=0.0049, respectively). Conclusion: Both Glut-1 expression and hexokinase activity were contributing factors related to F-18-FDG accumulation in human cancer cell lines. The relative contribution of Glut-1 expression and hexokinase activity, however, was different among different cancer cell types.

• Journal of Life Science
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• v.33 no.12
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• pp.1002-1014
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• 2023

The root of Cirsium japonicum var. maackii (Maxim.) has long been used in traditional medicine to prevent the onset and progression of various diseases and has been reported to exert a wide range of physiological effects, including antioxidant activity. However, research on its effects on hepatocytes remains scarce. This study used the human hepatocellular carcinoma HepG2 cell line to investigate the antioxidant activity of ethanol extract of C. japonicum root (EECJ) on hepatocytes. Hydrogen peroxide (H₂O₂) was used to mimic oxidative stress. The results showed that EECJ significantly reverted the decrease in cell viability and suppressed the release of lactate dehydrogenase in HepG2 cells treated with H₂O₂. Moreover, an analysis of changes in cell morphology, flow cytometry, and microtubule-associated protein light chain 3 (LC3) expression showed that EECJ significantly inhibited HepG2 cell autophagy induced by H₂O₂. Furthermore, it attenuated H₂O₂-induced apoptosis and cell cycle disruption by blocking intracellular reactive oxygen species and mitochondrial superoxide production, indicating strong antioxidant activity. EECJ also restored the decreased levels of intracellular glutathione (GSH) and enhanced the expression and activity of superoxide dismutase and GSH peroxidase in H₂O₂-treated HepG2 cells. Although an analysis of the components contained in EECJ and in vivo validation using animal models are needed, these findings indicate that EECJ is a promising candidate for the prevention and treatment of oxidative stress-induced liver cell damage.

• Journal of the Korean Society of Radiology
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• v.81 no.1
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• pp.166-175
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• 2020

Purpose This study aimed to compare the image quality and adverse events between Iopamidol 250 and Ioversol 320 usage during transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Materials and Methods Medical records and hepatic angiography from 113 patients who underwent TACE with Iopamidol 250 (44 patients) and Ioversol 320 (69 patients) were retrospectively reviewed. Vessel perception on hepatic angiography was graded into three categories by two radiologists for hepatic subsegmental arteries, the right gastroepiploic artery, right gastric artery, and pancreaticoduodenal artery. Imaging concordance was assessed by comparing the number of detected HCCs on hepatic angiography and CT. The adverse events before and after hepatic angiography were evaluated. Results The mean vessel perception scores were 2.92 and 2.94 for Iopamidol 250 and Ioversol 320, respectively. The imaging concordance was 31 (70.5%) and 46 (66.7%) patients for Iopamidol 250 and Ioversol 320, respectively. There were no statistical differences in vessel perception or imaging concordance (p > 0.05). One and six patients experienced nausea for Iopamidol 250 and Ioversol 320, respectively. There was no statistical difference in adverse events (p = 0.24). Conclusion Iopamidol 250 can be used in hepatic angiography for TACE without significant difference in image quality or occurrence of adverse events from Ioversol 320.

• Korean Journal of Radiology
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• v.2 no.1
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• pp.28-36
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• 2001

Objective: To provide a systematic overview of the effects of various parameters on contrast enhancement within the same population, an animal experiment as well as a computer-aided simulation study was performed. Materials and Methods: In an animal experiment, single-level dynamic CT through the liver was performed at 5-second intervals just after the injection of contrast medium for 3 minutes. Combinations of three different amounts (1, 2, 3 mL/kg), concentrations (150, 200, 300 mgI/mL), and injection rates (0.5, 1, 2 mL/sec) were used. The CT number of the aorta (A), portal vein (P) and liver (L) was measured in each image, and time-attenuation curves for A, P and L were thus obtained. The degree of maximum enhancement (Imax) and time to reach peak enhancement (Tmax) of A, P and L were determined, and times to equilibrium (Teq) were analyzed. In the computed-aided simulation model, a program based on the amount, flow, and diffusion coefficient of body fluid in various compartments of the human body was designed. The input variables were the concentrations, volumes and injection rates of the contrast media used. The program generated the time-attenuation curves of A, P and L, as well as liver-to-hepatocellular carcinoma (HCC) contrast curves. On each curve, we calculated and plotted the optimal temporal window (time period above the lower threshold, which in this experiment was 10 Hounsfield units), the total area under the curve above the lower threshold, and the area within the optimal range. Results: A. Animal Experiment: At a given concentration and injection rate, an increased volume of contrast medium led to increases in Imax A, P and L. In addition, Tmax A, P, L and Teq were prolonged in parallel with increases in injection time The time-attenuation curve shifted upward and to the right. For a given volume and injection rate, an increased concentration of contrast medium increased the degree of aortic, portal and hepatic enhancement, though Tmax A, P and L remained the same. The time-attenuation curve shifted upward. For a given volume and concentration of contrast medium, changes in the injection rate had a prominent effect on aortic enhancement, and that of the portal vein and hepatic parenchyma also showed some increase, though the effect was less prominent. A increased in the rate of contrast injection led to shifting of the time enhancement curve to the left and upward. B. Computer Simulation: At a faster injection rate, there was minimal change in the degree of hepatic attenuation, though the duration of the optimal temporal window decreased. The area between 10 and 30 HU was greatest when contrast media was delivered at a rate of 2 3 mL/sec. Although the total area under the curve increased in proportion to the injection rate, most of this increase was above the upper threshould and thus the temporal window was narrow and the optimal area decreased. Conclusion: Increases in volume, concentration and injection rate all resulted in improved arterial enhancement. If cost was disregarded, increasing the injection volume was the most reliable way of obtaining good quality enhancement. The optimal way of delivering a given amount of contrast medium can be calculated using a computer-based mathematical model.

• 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.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.5
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• pp.383-393
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• 2008

Purpose: Cancer specific killing can be achieved by therapeutic gene activated by cancer specific promotor. Expression of sodium iodide symporter (NIS) gene causes transportation and concentration of iodide into the cell, therefore radioiodine treatment after NIS gene transfer to cancer cell could be a form of radionuclide gene therapy. luciferase (Luc) gene transfected cancer cell can be monitored by in vivo optical imaging after D-luciferin injection. Aims of the study are to make vector with both therapeutic NIS gene driven by AFP promoter and reporter Luc gene driven by CMV promoter, to perform hepatocellular carcinoma specific radiodiodine gene therapy by the vector, and assessment of the therapy effect by optical imaging using luciferase expression. Materials and Methods: A Vector with AFP promoter driven NIS gene and CMV promoter driven Luc gene (AFP-NIS-CMV-Luc) was constructed. Liver cancer cell (HepG2, Huh-7) and non liver cancer cell (HCT-15) were transfected with the vector using liposome. Expression of the NIS gene at mRNA level was elucidated by RT-PCR. Radioiodide uptake, perchlorate blockade, and washout tests were performed and bioluminescence also measured by luminometer in these cells. In vitro clonogenic assay with 1-131 was performed. In vivo nuclear imaging was obtained with gamma camera after 1-131 intraperitoneal injection. Results: A Vector with AFP-NIS-CMV-Luc was constructed and successfully transfected into HepG2, Huh-7 and HCT-15 cells. HepG2 and Huh-7 cells with AFP-NIS-CMV-Luc gene showed higher iodide uptake than non transfected cells and the higher iodide uptake was totally blocked by addition of perchlorate. HCT-15 cell did not showed any change of iodide uptake by the gene transfection. Transfected cells had higher light output than control cells. In vitro clonogenic assay, transfected HepG2 and Huh-7 cells showed lower colony count than non transfected HepG2 and Huh-7 cells, but transfected HCT-15 cell did not showed any difference than non transfected HCT-15 cell. Number of Huh-7 cells with AFP-NIS-CMV-Luc gene transfection was positively correlated with radioidine accumulation and luciferase activity. In vivo nuclear imaging with 1-131 was successful in AFP-NIS-CMV-Luc gene transfected Huh-7 cell xenograft on nude mouse. Conclusion: A Vector with AFP promoter driven NIS and CMV promoter driven Luc gene was constructed. Transfection of the vector showed liver cancer cell specific enhancement of 1-131 cytotoxicity by AFP promoter, and the effect of the radioiodine therapy can be successfully assessed by non-invasive luminescence measurement.