^(131)I-Herceptin放射免疫显像用于Herceptin相关心脏毒性机制的实验研究  

Mechanism of cardiotoxicity associated with Herceptin using ^(131)I-Herceptin radioimmunoimaging

作　　者：范义湘[1] 罗荣城[2] 高梅菊[1] 刘青竹[1] 李科斌[1] 吴继珍[1] 石卫民[1] 

机构地区：[1]广东省第二人民医院核医学科,广东广州510317 [2]南方医科大学南方医院肿瘤中心,广东广州510515

出　　处：《南方医科大学学报》2009年第12期2477-2479,2484,共4页Journal of Southern Medical University

基　　金：广东省自然科学基金(037050)

摘　　要：目的探讨Herceptin相关心脏毒性的机制。方法131I-Herceptin采用Iodogen法制备。取家兔5只,注射131I-Herceptin 3h～5d,以放射免疫显像观察Herceptin的分布,以肌肉为参照,计算并比较各组织、器官的计数与肌肉计数的比值(O/M)。于注射后第5天处死家兔,取心、肺等组织,称重并测定放射性计数,计算并比较每克组织摄取分数(%ID/g)。以免疫组化测定并比较家兔各脏器HER2表达。结果注射后3h心脏O/M比值显著高于肺(P=0.032)和肝(P=0.019),但24h后显著降低(P=0.001)。各组织器官的每克组织的摄取分数以血液最高,为12.6%ID/g;其次为肝,为8.6%ID/g;心肌、肺和脾的摄取分数相近;肌肉最低,为1.6%ID/g。血液的摄取分数与其它脏器比较,除肝脏外(P=0.098),其它均显著低于血液。心肌摄取仅高于肌肉(P=0.041)和小肠(P=0.034),数值上甚至低于肝、肾、脾。心肌、肺和脾的摄取分数相近。心肌HER2表达水平与肝、肺、肾等组织未见显著差异(H=3.236,P=0.172)。结论心肌属于HER2低表达组织,对Herceptin的摄取量并不高于其它组织器官。Objective To study the mechanism of cardiotoxicity associated with Herceptin. Methods Herceptin was labeled with iodine-131 using the Iodogen method. Radioimmunoimaging was performed in 5 rabbits at 3 h to 5 days following ^131I-Herceptin injection to investigate the biodistribution of Herceptin. ^131I-Herceptin uptake in each organ or tissue relative to that in the muscular tissue （O/M ratio） was calculated and compared. On the fifth day following the injection, the organs including the heart, lung, liver and muscles were taken for measurement of the weight and radiocounts. HER2 expression was measured by immunohistochemistry in these organs and tissues. Results The O/M ratio of the heart was significantly higher than that of the lung （P=0.032） and liver （P=0.019） at 3 h after Herceptin injection, but educed significantly at 24 h （P=0.001）. The uptake of 131I-Herceptin in the myocardium was slightly higher that that in the muscle and intestine, but lower than that in the lung and spleen. HER2 expression showed no significant difference between the myocardium and the other tissues such as the liver, lung, and kidney （H=3.236, P=0.172）. Conclusion Myocardium expresses low levels of HER2 and accumulates Herceptin no more than the other tissues.

关 键 词：HERCEPTIN 心脏毒性 放射免疫显像 免疫组织化学染色 

分 类 号：R817.4[医药卫生—影像医学与核医学]