靶向纳米造影剂C225-USPIO标记裸鼠鼻咽癌移植瘤MR成像研究

Studies on MR Imaging of Nude Mice Bearing Nasopharyngeal Carcinoma Xenograft by Using Targeted Nano-Contrast Agent C225-USPIO

目的:制备针对EGFR的靶向纳米造影剂C225-USPIO,并检测其标记裸鼠鼻咽癌移植瘤MR成像(MRI)能力。方法:将西妥昔单抗(C225)与USPIO结合成C225-USPIO;检测造影剂粒径;选择EGFR高表达的鼻咽癌SUNE1 5-8F细胞株,接种于12只裸鼠的大腿腹侧皮下,待瘤直径增长至5mm时,随机分实验组和对照组各6只,将C225-USPIO或USPIO通过鼠尾静脉注射,于注射后0、8、24、72 h经磁共振成像仪行T2WI扫描;检测肿瘤组织内造影剂分布。结果:C225-USPIO粒径约45～50 nm;MRI示实验组8 h T2值较0 h略降低(P>0.05),24 h显著降低(P<0.05),72 h无明显改变(P>0.05)。对照组8～72 h各时间点T2值与0 h相比无明显改变(P>0.05);注射造影剂72 h后肿瘤组织未见明显铁颗粒。结论:C225-USPIO颗粒可通过毛细血管,并能运用于体内磁共振分子成像,可以降低裸鼠移植瘤磁共振T2信号强度,具有一定的特异性和靶向性。

Objective： This work aimed to design epidermal growth factor receptor-targeted contrast agent C225-USPIO and to evaluate its magnetic resonance imaging （MRI） capability to mark the nasopharyngeal carcinoma xenograft in nude mice. Methods： C225-USPIO was designed by conjugating ultra-small superparamagnetic iron oxide （USPIO） nanoparticles with cetuximab （C225）. The diameter of C225-USPIO was detected. Nasopharyngeal carcinoma cells SUNE1 5-8F with EGFR overexpression were transplanted into the ventral subcutaneous site of the right rear thigh of 12 nude mice. When the diameter of a transplanted tumor reached 5 mm, the nude mice were randomly divided into two groups, i.e., the experiment group （Group One） and the control group （Group Two）, with 6 mice in each group. C225-USPIO and USPIO were separately injected into the mice through the caudal vein. MRI T2 weighted image （T2WI） scanning was conducted 0, 8, 24 and 72 h after the injection. The nano-contrast agent distribution in the tumor tissues was detected. Results： The diameter of the contrast agent ranged from 45 nm to 50 nm. MR/results showed that compared with the value of T2WI signal intensity 0 h after the contrast agent injection, the T2 value of the xenograft tumor in Group One was slightly decreased 8 h after the injection （P〉0.05）. The value was significantly decreased 24 h after the injection （P〈0.05）, and no apparent change in the T2 value was observed 72 h after the injection （P〉0.05）. In Group Two, no significant changes in the T2 value of xenograft tumor after the USPIO injection were observed at each time point. No significant iron particles were found in the tumor tissue 72 h after the injection. Conclusion： C225-USPIO particles could pass through blood capillaries and could be applied for MR imaging in vivo. In addition, they can reduce MRI T2 signal intensity of the xenograft in nude mice with a certain specificity and targeting property.