HER-2受体放射性配体99Tcm-TP1623的制备及其在正常动物体内的分布

Preparation of 99Tcm-TP1623 targeting at HER-2 receptor and its distribution in animals

目的 探讨HER-2受体放射性配体99Tcm-B2-S22-AFA（99Tcm-TP1623）在健康小鼠体内的生物分布和健康家兔体内的动态显像分布.方法 采用氯化亚锡间接法9 9Tcm标记TP1623,3MM色谱纸层析测定9 9Tcm-TP1623标记率,计算其比活度;通过体外稳定性实验、血清蛋白结合实验和油/水分配实验,鉴定标记产品理化性质;研究99Tcm-TP1623于1、5、10、30、60和120 min在健康小鼠体内的生物分布特性;通过SPECT显像,结合感兴趣区（ROI）时间-放射性曲线分析,观察99Tcm-TP1623在健康家兔体内的动态分布变化.结果 99Tcm-TP1623标记率为（96.4±0.1）％,比活度为（24.35±0.06） TBq/mmol,室温下放置6h后放化纯度为（95.03±0.97）％.油/水分配系数P为-（2.51±0.15）.小鼠血液放射性清除快,通过肾脏排泄较快,心、肺、肝、肌肉、骨骼等放射性随时间延长逐渐减低,60 min后放射性呈明显低水平,肠道放射性则随时间缓慢增加.脑放射性始终呈最低水平.健康家兔体内99Tcm-TP1623血池影消退迅速,主要通过肾脏排泄,见胆囊、肠道排泄影,胃区和颈部未见放射性浓聚,脑组织始终呈低本底.结论 99Tcm-TP1623制备方法简便,标记率及产品比活度高,体内、外稳定性好,具有优良的动物体内动力学特性.

Objective To prepare 99Tcm-B2-S22-AFA （99Tcm-TP1623）and investigate its biodistribution and kinetic imaging in healthy animals.Methods TP-1623 was synthesized and labeled indirectly by 99Tcm using stannous chloride as the reductive agent.The labeling rate was determined with chromatography using Whatman 3MM filter paper and by calculating the specific activity.The biodistribution of 99Tcm-TP1623 was tested at 1,5,10,30,60,120 min after intravenous injection into mice.According to the SPECT images and the time response of the radioactivity in the region of interest （ROI）,the dynamic distribution of 99Tcm-TP1623 was assayed.Results The radiolabeling rate of 99Tcm-TP1623 was （96.4-± 0.1） % and the specific activity was （24.35 ± 0.06） TBq/mmol.After being conserved at room temperature for 4 h,the radiochemical purity of 99Tcm-TP1623 was （95.03 ± 0.97） %.The oil-water distribution coefficient was-（2.51 ± 0.15）.The bio-distribution test showed that the radioactivity in mice blood disappeared very fast over time by a quick excretion through renal.Meanwhile,the radioactivities in the heart,lung,liver,muscle and bone of mice decreased gradually along time and after 60 min they approached to the lowest levels.The radioactivity in brain always kept at a low level,but the radioactivity in intestinal increased slowly.For rabbits,the SPECT images showed that the radioactivity in blood disappeared quickly and the radioactivities were eliminated through kidneys.Meanwhile there were excretion images in gallbladder and intestinal,but no obvious nuclide accumulation in thyroids and stomach,and low radioactivity in brain as well.Conclusions 99Tcm-TP1623 is easy to prepare and has a high radiolabeling efficiency and good stability in vivo and in vitro,and it has excellent dynamic characteristics in normal animals.