^(125)I-OxLDL-Ab在正常小鼠及动脉粥样硬化动物模型体内的生物分布  

Biodistribution of ^(125)I-OxLDL-Ab in Normal Mice and in Animal Models of Atherosclerosis in Vivo

作　　者：刘子华[1] 樊彩云[1] 李凤林[1] 邓新荣[1] 徐燕华 罗志福[1] 

机构地区：[1]中国原子能科学研究院同位素研究所,北京102413 [2]成都华神生物技术有限责任公司,四川成都610225

出　　处：《核化学与放射化学》2016年第6期378-384,共7页Journal of Nuclear and Radiochemistry

摘　　要：分别采用高效液相色谱法、紫外分光光度法对OxLDL-Ab进行定性、定量分析,评价^(125)I-OxLDL-Ab在正常动物和动脉粥样硬化模型动物的体内分布。正常动物采用昆明小鼠,模型采用载脂蛋白E基因敲除的小鼠(apolipoprotein E-deficient mice,ApoE^(-/-))。高效液相色谱条件为:磷酸缓冲液(PB,0.2 mol/L,pH=7.4)为流动相,流速1.0mL/min,检测波长220nm;紫外分光光度法测得蛋白浓度的标准曲线为:y=0.664 5x-0.008 3,r2=0.999 7。^(125)I-OxLDL-Ab在正常小鼠体内分布实验结果表明:除甲状腺外,各器官的放射性摄取随时间延长而减少,无明显浓集;在注射^(125)I-OxLDL-Ab后1d各器官代谢消除超过2/3,7d后血液中完全清除。^(125)I-OxLDL-Ab在ApoE^(-/-)鼠体内的分布实验中采用w=2%的KI溶液封闭了甲状腺,消除了甲状腺高摄取的影响;靶器官肺有较高放射性摄取,且在注射后4~8h显示出放射性浓集;除血外,其它各器官的靶器官/非靶器官的放射性摄取比值(T/NT)均大于1,其中T/Mu(肌肉)>8,显示出^(125)I-OxLDL-Ab对靶器官有一定的选择性。标记抗体的体内靶向性是显像研究中至关重要的一环,要进一步用于动脉粥样硬化早期显像诊断,还需进一步提高靶器官/非靶器官的放射性摄取比值,提高其在体内与其抗原的亲和性。Anti-oxidized low-density lipoprotein antibody（OxLDL-Ab） was analysized with high performance liquid chromatography （HPLC） and ultraviolet spectrophotometry （UV）. The biodistribution of 125 I-OxLDL-Ab was evaluated in both normal animals and animal mod- els of atherosclerosis. Kunming mice were （ApoE-/- mice） were used as animal models used as normal animals and ApoE knock-out mice of atherosclerosis in the study of biodistribution.The optimum conditions of HPLC were as follows： phosphate buffer （0. 2 mol/L, pH=7.4） was used as the mobile phase, the flow rate was 1 mL/min and the detection wavelength was 220 nm. The standard curve of concentration was obtained in the quantitative analysis of UV with y= 0. 664 5x- 0. 008 3 （r2 = 0. 999 7）. Biodistribution in normal animal show that organ uptakes decrease with time and no obvious accumulation is observed in organs except hypothyroid; over 2/3 uptake clear away in 24 h after injection and couldn＇t be detected 7 d later. The hypothyroids of ApoE-/ mice are blocked by 2% KI solution to avoid their high uptake in the biodistribution of 12aI-OxLDL-Ab. Uptake in lung （the target organ） is high in the early 4-8 h after injection of 125I-OxLDL-Ab. The ratio of target/organs is more than 1 except blood, and the ratio of target/muscle is more than 8, which show the selectivity of 125I-OxLDL-Ab to the targeted organ in vivo. Futher studies need to be done to evaluate the possibility 125 I-OxLDL-Ab as a SPECT imaging agent in diagnose of early stage of atherosclerosis.

关 键 词：氧化低密度脂蛋白单克隆抗体 动脉粥样硬化 125I APOE-/-小鼠 生物分布 

分 类 号：TL923[核科学技术—核燃料循环与材料]