用于原位人胶质母细胞瘤模型中突变型 EGF 受体成像的 MR 信号放大。
MR signal amplification for imaging of the mutant EGF receptor in orthotopic human glioma model.
机构信息
Department of Radiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA.
出版信息
Mol Imaging Biol. 2013 Dec;15(6):675-84. doi: 10.1007/s11307-013-0653-8.
PURPOSE
To investigate the potential of targeted MR signal amplification strategy for imaging of EGF receptor variant III (EGFRvIII) overexpression associated with the infiltrating margin of aggressive orthotopic brain tumors.
PROCEDURES
F(ab')2 fragments of humanized anti-EGFRvIII monoclonal antibody (EMD72000) were linked to deglycosylated horseradish peroxidase (HRP) and glucose oxidase (GOX). Detection of the F(ab')2 conjugate pair colocalization in vivo was enabled by a subsequent IV injection of a low molecular weight paramagnetic substrate of HRP, diTyr-GdDTPA.
RESULTS
The delivery of the targeted fragments to the tumor was validated using SPECT/CT imaging of radiolabeled anti-EGFRvIII F(ab')2 conjugates. Further, by using 3 T MRI, we observed time-dependent differences in tumor signal intensity and signal retention at the endpoint depending on whether or not the animals were pre-injected with the anti-EGFRvIII F(ab')2 conjugates.
CONCLUSIONS
Imaging of EGFRvIII expression in vivo was enabled by consecutive administration of targeted F(ab')2 conjugates and a paramagnetic substrate resulting in a tumor-specific receptor detection with high specificity and resolution.
目的
研究靶向磁共振信号放大策略在成像表皮生长因子受体变异 III（EGFRvIII）过表达中的潜力，该过表达与侵袭性原位脑肿瘤的浸润边缘有关。
过程
将人源化抗 EGFRvIII 单克隆抗体（EMD72000）的 F(ab')2 片段与去糖基化辣根过氧化物酶（HRP）和葡萄糖氧化酶（GOX）连接。通过随后静脉注射 HRP 的低分子量顺磁底物二酪氨酸-GdDTPA，实现了 F(ab')2 缀合物对体内共定位的检测。
结果
使用放射性标记的抗 EGFRvIII F(ab')2 缀合物的 SPECT/CT 成像验证了靶向片段向肿瘤的递呈。此外，通过使用 3T MRI，我们观察到根据动物是否预先注射抗 EGFRvIII F(ab')2 缀合物，肿瘤信号强度和终点处的信号保留存在时间依赖性差异。
结论
通过连续给予靶向 F(ab')2 缀合物和顺磁底物，实现了体内 EGFRvIII 表达的成像，从而具有高特异性和分辨率的肿瘤特异性受体检测。
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