^(131)I-Herceptin的制备、质控及在新西兰兔的生物分布

Preparation,quality control and biodistribution of ^(131)I-herceptin in New Zealand rabbits

目的探讨131I-Herceptin的免疫活性、生物分布及代谢规律,为乳腺癌的131I-Herceptin放射免疫治疗提供实验依据。方法①采用Iodogen法对Herceptin进行131I标记,以HPLC法测定放射化学纯度(RCP)。以与BT-474细胞结合率(BR)鉴定131I-Herceptin的免疫活性。②按74 MBq/kg.b.w.对3只新西兰兔注射131I-Herceptin,注射后3 h及第1、3、5天进行透射CT显像。以肌肉为参照,计算各脏器放射性计数比值(O/M)。③第5天处死动物,取血、心、肺、肝、肾等脏器,计算每克组织摄取分数(ID%/g),对结果进行统计分析。结果131I-Herceptin的标记率为93%,RCP为95%,在BT-474细胞结合率为(36.9±4.7)%。注射131I-Herceptin后不同时间均以心脏、肺、肝浓聚显著,肌肉、肠影像稀疏。随时间延迟,心影逐渐稀疏,肝脏影像浓聚。注射后3 h,心脏O/M值显著高于肺及肝、肾、肠等脏器。随时间延迟,心脏O/M值于注射后1 d显著降低(t=10.817,P<0.001),第3、5天亦显著降低,肝脏O/M值在第1、3、5天均比注射后3 h显著下降。每克组织的摄取分数以血液最高,为(11.3 ID/g)%、肝为(2.8 ID/g)%、心肌仅为(1.8 ID/g)%。结论131I-Herceptin的免疫活性高。机体分布以血液、肝、肾为主,心肌摄取量低。

Objective To study the immunoactivity,biodistribution and metasbolic pattern of ^131I-Herceptin in rabbits. Methods Herceptin was radiolabelled with ^131I and its radiochemiealpurity （RCP） measured by size-exclusion high-pressure liquid chromatography （HPLC）. The binding rate to BT-474 cells was measured to evaluate the immunoactivity of ^131I-Herceptin. ^131I-herceptin （2.0 mCi/kg） was injected intravenously into New Zealand rabbits. Scintigraphy on emission computed tomography was performed at 3 h, 1, 3 and 5 days after injection, and the radiocounts of the heart, liver and kidney etc. were compared with that of the muscle to calculate the organ-to-muscle activity ratio （O/M）. On the fifth day,the rabbits were killed and the blood, myocardium, lung and other organs were obtained for measuring the radiocounts on γ-counter to calculate the uptake percentage per gram tissue 0D%/g）. Results The labeling rate of ^131I-herceptin was 93% with RCP of 95% and binding rate to BT-474 cells of 36.9%. After injection of ^131I-herceptin, the heart, lung and liver displayed dense radioactive regions but not the muscles and intestines. Three hours after injection, the O/M ratio of the heart was significantly higher than that of the lung, kidney and intestine （P〈0.05）, but decreased significantly one day after injection （t= 10.817, P〈0.001） with further decrement on days 3 and 5 （P〈0.05）. The O/M ratio of liver on day 1, 3, and 5 reduced significantly in comparison with that at 3 h （P〈0.05）. The uptake percentage was higher in the blood （11.3 ID/g%） than in the liver （2.8 ID/g%） and the myocardium （1.8 ID/g%）. Conclusions ^131I-herceptin possesses high immunoactivity which distributes mainly in the blood, liver and kidney, but with low uptake in the myocardium.