| 1. The development of carbon tetrachloride-induced hepatic fibrosis model in mouseObjective To develop a simple way to establish hepatic fibrosis model in mouse for performing preclinical study of animal positron emission tomography (PET) imaging of Fluorine-18labeled galactosyl-neoglycoalbumin ([18F]FNGA).Methods6-7weeks aged female Kunming mice were intraperitoneal injected with carbon tetrachloride,0.4ml10%, every48hours for42days. The hepatic injuries were evaluated with measurements of serum markers and pathological examinations.Results Compared with normal group, serum level of total protein and cholinesterase were lower (p<0.001and0.05, respectively), while serum level of alkaline phosphatase was higher (p<0.05) in model group. Also, serum level of total protein, albumin, and cholinesterase were lower (p<0.05,0.05, and0.01, respectively) in model group compared to control group. The pathological examinations of the model group showed significant fibrosis of interlobular septa, dilation of centrilobular veins, severe focal necrosis of intralobular hepatocytes, and considerable psammoma bodies calcification.Conclusion A successive method to induce mouse hepatic fibrosis was developed. 2. Application of [18F]FNGA in hepatic fibrosis model of mouseObjective To identify the uptake, metabolism, excretion, and biodistribution of [18F]FNGA in different models amongst different time and to validate its biological effectiveness.Methods Mice in hepatic fibrosis model group and control group both were divided into three subgroups randomly. The mice were injected [18F]FNGA into vena caudalis and sacrificed at5min,30min, and1h later, respectively. Important organs including liver, heart, lung, kidney, brain, et al. were taken immediately. Subsequently, the counters of radioactivity in the organs above were measured.Results [18F]FNGA was accumulated in the liver in all six subgroups. The radioactivity in blood which was higher at5min, decreased so rapidly that much lower at 30min. The radioactivity of urine was significantly higher than that of liver in both control group and model group (p<0.05and0.001, respectively) at30min, and in control group (p<0.05) at1h.Conclusion [18F]FNGA was accumulated in the liver for a long time which is enough for imaging. The metabolites excreted mainly through the kidney to the urinary bladder. The uptake, metabolism, and excretion of [18F]FNGA were related to liver function. 3. Preclinical study of animal imaging of [18F]FNGAObjective To demonstrate that [18F]FNGA displayed good properties for animal imaging. To observe the metabolism of [18F]FNGA in vivo and explore the index which may be used in evaluation of liver function.Methods Mice in hepatic fibrosis model group and control group both were divided into two subgroups randomly. The MicroPET scan was performed for30min and1h, respectively. The blood samples were taken and the serum markers were measured, immediately. Subsequently, process the data acquired and outline the regions of interests through supporting software of MicroPET. Then calculate the index as follows:Liver Uptake Ability (LUA), Time at Peak (tP), a thousand fold of uptake rate (LK1000), and NGA Clearance index (CI).Results The animal imaging of [18F]FNGA was satisfied. Among the index, LUA and LK1000was higher in control group (p<0.05), while tp was lower (p<0.01) compared to hepatic fibrosis model group. LUA correlated with serum level of total protein (r=0.559, p=0.038); tp correlated with serum level of total protein (r=-0.632, p=0.015) and glucose (r=0.719, p=0.029); LK1000was correlated with serum level of glucose (r=-0.730, p=0.025) and total bilirubin acid (r=-0.690, p=0.006).Conclusion [18F]FNGA had initial high activity accumulation in the liver. High liver/background ratio affords promising biological properties to get clear images. The index may be useful for evaluation of liver function. |
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