| 张炜华,郑双双,姚秀忠,杜斌,翁伟宇.荷钆硬脂酰壳寡糖的制备及其在胰腺癌成像中的应用[J].中国医学影像技术,2017,33(4):499~503 |
| 荷钆硬脂酰壳寡糖的制备及其在胰腺癌成像中的应用 |
| Preparation of gadolinium-loaded stearic acid grafted chitooligosaccharide and application in pancreatic tumor imaging |
| 投稿时间：2016-09-30 修订日期：2017-01-05 |
| DOI：10.13929/j.1003-3289.201609159 |
| 中文关键词: 钆 壳寡糖 胶束 磁共振成像 胰腺肿瘤 |
| 英文关键词:Gadolinium Chitooligosaccharide Micelles Magnetic resonance imaging Pancreatic neoplasms |
| 基金项目:上海市自然科学基金（16ZR1405900）。 |
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| 中文摘要: |
| 目的 制备荷钆硬脂酰壳寡糖（COSSA-DTPA-Gd），评价其胶束性质、细胞毒性、体外弛豫率和在胰腺肿瘤中的MR成像效果。方法 利用酰化反应合成硬脂酰壳寡糖，再枝接螯合剂DTPA并与Gd3+螯合得到最终产物。采用电镜和激光粒度仪等测定产物胶束性质；噻唑蓝法测定产物细胞毒性；在MR上测定体外弛豫率，评估其在原位胰腺肿瘤成像强化中的效果。结果 合成的COSSA-DTPA-Gd在水中可自发形成胶束，临界胶束浓度为（5.12±0.43）μg/ml，外观近似球形，粒径（58.3±5.7）nm，带正电荷，含钆量为330.31 μmol/g。产物的细胞毒性与市售对比剂马根维显相似（P>0.05），24 h内细胞存活率>85%。COSSA-DTPA-Gd的体外纵向弛豫率为8.23 mM-1·s-1，静注后对胰腺肿瘤的成像效果优于马根维显，肿瘤周边首先强化，肿瘤内部渐进性强化。结论 COSSA-DTPA-Gd胶束对比剂对胰腺肿瘤具有良好的成像效果。 |
| 英文摘要: |
| Objective To prepare gadolinium-loaded stearic acid grafted chitooligosaccharide (COSSA-DTPA-Gd) and evaluate its micelle properties, cytotoxicity, relaxation rate in vitro, and pancreatic tumor in vivo imaging. Methods Stearic acid grafted chitooligosaccharide (COSSA) was synthesized by acetylation reaction between stearic acid and chitooligosaccharide. Diethylenetriaminepentaacetic dianhydride (DTPA) was conjugated to the residual amino groups of COSSA, then Gd3+ was chelated to obtain the final product. The micelle properties were measured using an electron microscopy and a laser particle sizer. The MTT assay was adopted to determine cytotoxicity. The in vitro relaxation rate and in vivo imaging of pancreatic tumor were evaluated using an MR scanner. Results COSSA-DTPA-Gd could self-assemble into stable micelles in aqueous solutions with a critical micelle concentration of (5.12±0.43)μg/ml. The micelles had positive charge and exhibited roughly spherical shape with a mean diameter of (58.3±5.7)nm. The content of Gd3+ in COSSA-DTPA-Gd was 330.31 μmol/g. The nanoprobe and Magnevist, the commercial formulation, showed similar cytotoxicity (P>0.05). The cell survival rate within 24 h were higher than 85%. The in vitro relaxation rate of COSSA-DTPA-Gd was 8.23 mM-1·s-1. After intravenous injection, COSSA-DTPA-Gd showed a better positive contrast-enhancing effect for pancreatic tumor than Magnevist. The MR images at the tumor periphery was rapidly enhanced, while a slow increase in image quality was observed in tumor core. Conclusion The prepared COSSA-DTPA-Gd can be used for efficient MR imaging of pancreatic tumor. |
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