Monoclonal antibody to cardiac myosin: imaging of experimental myocardial infarction.

Monoclonal antibody to cardiac myosin: imaging of experimental myocardial infarction.
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DOI:
10.1089/hyb.1984.3.11
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发表时间:
1984
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通讯作者:
B. Khaw;J. Mattis;G. Melincoff;H. Strauss;H. Gold;E. Haber
B. Khaw;J. Mattis;G. Melincoff;H. Strauss;H. Gold;E. Haber
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作者:
B. Khaw;J. Mattis;G. Melincoff;H. Strauss;H. Gold;E. Haber

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用与犬心肌肌球蛋白发生交叉反应的抗人心肌肌球蛋白的单抗R11D10对实验性心肌梗死模型进行体内定位和显像。R11D10 Fab的Ka为5×10(8)M~(-1),通过双功能络合剂二乙三胺五乙酸(DTPA),用高铁酸锶二亚硫酸盐还原法制备了99m~(-1)的~(99m)Tc。99mTcR11D10Fab在脑梗塞灶内的摄取最早在静脉给药后2小时即可见。与~(125)I标记的多克隆抗肌球蛋白Fab相比,~(125)I标记的多克隆抗肌球蛋白Fab对R11D10的摄取与~(125)I标记的多克隆抗肌球蛋白Fab的摄取呈负相关(r=-0.75,-0.87,-0.89)。心肌梗死区R11D10Fab与正常心肌R11D10Fab的比值高达30:1,抗体对抗原的进入不受血流限制。然而,在严重血流受限的情况下,这一比例较低,约为10:1。尽管理论上每个肌球蛋白分子可与R11D10 Fab结合一个表位的限制,但梗死心肌中大量的肌球蛋白允许足够的放射性标记R11D10浓度,用于通过外部伽马闪烁扫描显示心肌梗死。
Monoclonal antibody R11D10 to human cardiac myosin, which also cross-reacted with canine cardiac myosin, was used to demonstrate in vivo localization and visualization by gamma scintigraphy of experimental myocardial infarction. R11D10 Fab with a Ka of 5 X 10(8) M-1 was labeled with technetium-99m (99mTc) by the dithionite reduction method of technetium pertechnetate, via a bifunctional chelating agent, diethylene triamine pentaacetic acid (DTPA). Uptake of 99mTc R11D10 Fab in the infarct can be visualized as early as 2 h after intravenous administration. Comparison of R11D10 uptake to thallium-201, an analogue of potassium which is sequestered by normal myocardium, showed an inverse relation (r = -0.75, -0.87, -0.89), similar to that obtained with 125I labeled polyclonal antimyosin Fab. Ratios of R11D10 Fab in the infarct to normal myocardium were as high as 30:1 where access of antibody to antigen was not blood flow limited. However, with severe blood-flow restriction, the ratios were lower at about 10:1. Despite the theoretical limitation of a single epitope per myosin molecule available for binding by R11D10 Fab, the immense excess of myosin in the infarcted myocardium allowed adequate concentration of radiolabeled R11D10 for visualization of the infarct by external gamma scintiscanning.