荷钆硬脂酰壳寡糖的制备及其在胰腺癌成像中的应用

发布时间：2019-06-17 11:05

【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Gd~(3+)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330.31μmol/g。产物的细胞毒性与市售对比剂马根维显相似(P0.05),24h内细胞存活率85%。COSSA-DTPA-Gd的体外纵向弛豫率为8.23mM~(-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。
[Abstract]:Objective to prepare gadolinium stearyl chitosan oligosaccharide (COSSA-DTPA-Gd) and evaluate its micellar properties, cytotoxicity, relaxation rate in vitro and MR imaging effect in pancreatic tumors. Methods stearyl chitosan oligosaccharide was synthesized by acylation reaction, followed by grafting chelating agent DTPA and chelating with Gd~ (3) to obtain the final product. The micellar properties of the products were measured by electron microscope and laser particle size meter, the cytotoxicity of the products was determined by thiazole blue method, and the relaxation rate in vitro was measured on MR to evaluate the effect of the products in situ pancreatic tumor imaging enhancement. Results the synthesized COSSA-DTPA-Gd could form micelle spontaneously in water. The critical micelle concentration was (5.12 卤0.43) 渭 g 路ml, the appearance was approximately spherical, the particle size was (58.3 卤5.7) nm, with positive charge, and the content of gadolinium was 330.31 渭 mol / g. The cytotoxicity of the product was similar to that of the market contrast agent Ma Genwei (P 0.05). The longitudinal relaxation rate of cell survival rate 85%.COSSA-DTPA-Gd within 24 hours was 8.23 mm ~ (- 1) s ~ (- 1). The imaging effect of intravenous injection on pancreatic tumor was better than that of Magenway, the peripheral area of the tumor was first enhanced, and the internal enhancement of the tumor was gradual. Conclusion COSSA-DTPA-Gd micellar contrast agent has a good imaging effect on pancreatic tumors.
【作者单位】：华东理工大学药学院;复旦大学附属中山医院放射科;
【基金】：上海市自然科学基金(16ZR1405900)
【分类号】：R735.9

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