【摘要】 目的:评价靶向Endoglin的CL-PEG-MnFe₂O₄纳米胶束在肿瘤微血管和微淋巴管MR成像中的价值。方法:乳腺癌裸鼠移植瘤模型5只,经球后静脉注入铁浓度为50μg/m L靶向Endoglin的CL-PEG-Mn Fe₂O₄纳米微粒,总量0.15 m L。分别于对比剂注射后0、5、15、30、60和120 min进行SE T1WI、FSE T2WI、GRE T2*WI及T2mapping扫描。在各时间点测量肿瘤信号强度,绘制时间-信号强度变化曲线,分析曲线的变化规律。测量并计算肿瘤的T2值、R2值,评价CL-PEG-Mn Fe₂O₄探针的靶向增强效能,以非靶向的PEG-PCL-Mn Fe₂O₄纳米胶束为对照。结果:纳米粒注射后早期,肿瘤呈负性增强,肿瘤周边区明显;60 min后,注射非靶向PEG-PCL-MnFe₂O₄纳米胶束的肿瘤信号强度恢复到基线水平,而注射靶向CL-PEG-MnFe₂O₄纳米胶束的肿瘤周边区仍呈斑点状强化。CL-PEG-Mn Fe₂O₄和PEG-PCL-Mn Fe₂O₄注射前,注射后0、5、15、30、60、120 min肿瘤的T2值分别为（77.98±10.29）、（44.66±5.25）、（50.80±3.85）、（54.25±5.08）、（57.20±4.04）、（59.20±7.11）、（60.15±7.43）ms和（78.66±5.71）、（44.85±5.67）、（50.06±8.62）、（63.10±8.36）、（70.19±7.71）、（74.76±10.60）、（76.63±12.13）ms。CL-PEG-MnFe₂O₄的时间-信号强度变化率曲线呈下降-上升-平台型;PEG-PCL-Mn Fe₂O₄的时间-信号强度变化率曲线呈下降-上升型。结论:靶向Endoglin的CL-PEG-MnFe₂O₄纳米胶束能与肿瘤新生血管及新生淋巴管结合,并能通过MRI检测,为肿瘤新生血管和新生淋巴管的MR靶向显像提供了实验基础。更多还原

【Abstract】 Objective To evaluate the value of Endoglin targeted CL-PEG-MnFe₂O₄ nanomicelles in magnetic resonance（MR）imaging of tumor microvessels and lymphatic microvessels. Methods In 5 nude-mice breast cancer xenografts models, a total of 0.15 mL CL-PEG-MnFe₂O₄ nanomicelles with a concentration of 50 μg/mL was intravenously administrated by retrobulbar vein. MR imaging was performed at 0, 5, 15, 30, 60, 120 min after contrast injection. The MR imaging sequences included spin echo T1-weighted imaging（SE T1 WI）, fast spin echo T2-weighted imaging（FSE T2 WI）, gradient echo T2*-weighted imaging（GRE T2*WI） and T2 mapping. The tumor signal intensity was measured at each time point, and time-intensity curve was plotted to analyze the change rule of the curve. The T2 and R2 values of the tumor were measured and calculated, so as to evaluate the target enhancement performance of CL-PEG-MnFe₂O₄ nanomicelles. Non-targeted PEG-PCL-MnFe₂O₄ was served as a control. Results In the early period after the intravenous administration of nanomicelles, the tumor was negatively enhanced and the peripheral area of the tumor had obvious enhancement. At 60 min after the intravenous administration of targeted CL-PEG-MnFe₂O₄ nanomicelles, the tumor displayed patchy or spot-like enhancement, which was mainly limited to the peripheral areas of the tumor.However, the tumor signal intensity returned to the baseline at 60 min after the administration of non-targeted PEG-PCL-Mn Fe₂O₄ nanomicelles. The T2 values of the tumor before and at 0, 5, 15, 30, 60 and 120 min after the administration of CL-PEG-MnFe₂O₄ nanomicelles were（77.98±10.29）,（44.66±5.25）,（50.80±3.85）,（54.25±5.08）,（57.20±4.04）,（59.20±7.11） and（60.15±7.43） ms,respectively; and those values before and after the administration of PEG-PCL-Mn Fe₂O₄ nanomicelles were（78.66±5.71）,（44.85±5.67）,（50.06±8.62）,（63.10±8.36）,（70.19±7.71）,（74.76±10.60） and（76.63±12.13） ms, respectively. After the intravenous administration of CL-PEG-MnFe₂O₄ nanomicelles, the time-intensity curve was decreased firstly and then increased and finally reached a plateau, while the time-intensity curve after the intravenous administration of PEG-PCL-MnFe₂O₄ was decrease firstly and then increased. Conclusion Endoglin targeted CL-PEG-MnFe₂O₄ nanomicelles can bind to tumor microvessels and lymphatic microvessels, which can be detected by MR imaging, thereby providing an experimental basis for targeted MR imaging of tumor microvessels and lymphatic microvessels.更多还原