Zhu Yeqing, Ling You, Zhong Jinglian, Liu Xueguo, Wei Kun, Huang Suiqiao
Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Acta Radiol. 2012 Sep 1;53(7):812-9. doi: 10.1258/ar.2012.120040. Epub 2012 Jul 13.
Radiation-induced brain injury (RBI) is the most serious complication of primary and metastatic brain and neck malignant tumors following radiation therapy. However, at present, RBI is difficult to diagnose in the early period. Recently, studies have demonstrated that the early stage of RBI is characterized by an inflammatory reaction, and that intercellular adhesion molecule-1 (ICAM-1) is significantly up-regulated in the irradiated brain tissues.
To provide an early diagnosis of RBI using molecular magnetic resonance imaging (MRI) with microparticles of iron oxide (MPIO) targeted to ICAM-1 in the vascular endothelium of brains.
A monoclonal antibody against ICAM-1 was conjugated to MPIO to form the targeted MRI contrast agent ICAM-MPIO. The adhesion of ICAM-MPIO to endothelial cells was quantified by optical imaging and MRI. Sprague-Dawley rats were irradiated to establish an animal model of the early period of RBI. ICAM-MPIO and free-MPIO were injected via tail vein, respectively. T(2) signal intensity and T(2) values of the irradiated brains and normal brains were subsequently evaluated by MRI.
In vitro, the adhesion of ICAM-MPIO to the activated endothelial cells was 5 ± 0.5-fold greater than to the non-stimulated cells, which could be detected by optical imaging and MRI (R(2) = 1.0, P < 0.01). In vivo, ICAM-MPIO caused a marked negative MRI contrast effect in irradiated brains. As compared with brains without irradiation, the specific contrast effect increased more than seven-fold after administration of ICAM-MPIO (F = 751.495, P < 0.05).
MPIO coated with monoclonal antibody of ICAM-1 could be used for detecting the early period of RBI by optical imaging and MRI.
放射性脑损伤（RBI）是原发性和转移性脑及颈部恶性肿瘤放疗后最严重的并发症。然而，目前RBI在早期难以诊断。最近，研究表明RBI早期以炎症反应为特征，且细胞间黏附分子-1（ICAM-1）在受照射脑组织中显著上调。
利用靶向脑内血管内皮细胞ICAM-1的超顺磁性氧化铁微粒（MPIO）分子磁共振成像（MRI）对RBI进行早期诊断。
将抗ICAM-1单克隆抗体与MPIO偶联，形成靶向MRI造影剂ICAM-MPIO。通过光学成像和MRI对ICAM-MPIO与内皮细胞的黏附进行定量。对Sprague-Dawley大鼠进行照射，建立RBI早期动物模型。分别经尾静脉注射ICAM-MPIO和游离MPIO。随后通过MRI评估受照射脑和正常脑的T(2)信号强度及T(2)值。
体外实验中，ICAM-MPIO与活化内皮细胞的黏附比未刺激细胞高5±0.5倍，可通过光学成像和MRI检测到（R(2)=1.0，P<0.01）。体内实验中，ICAM-MPIO在受照射脑内引起明显的MRI负性对比效应。与未照射的脑相比，注射ICAM-MPIO后特异性对比效应增加了7倍多（F=751.495，P<0.05）。
包被ICAM-1单克隆抗体的MPIO可用于通过光学成像和MRI检测RBI早期。
