坏死亲和性MRI对比剂Gd-DO3A-rhein的合成及其靶向性

发布时间：2018-03-01 18:36

本文关键词： 大黄酸 Gd-DOA-rhein 坏死靶向性肝坏死磁共振成像　出处：《中国药科大学学报》2017年03期 　论文类型：期刊论文

【摘要】：以大黄酸为底物合成磁共振成像(MRI)对比剂并评价其坏死靶向性。经两步酰化和两步脱保护方法得到新的配体10-{[6-(1,8-二羟基蒽醌-3-甲酰氨基)己基]氨基}乙酰基-1,4,7,10-四氮杂环十二烷-1,4,7-三乙酸(DO3A-rhein),再与Gd3+配位得到顺磁性对比剂10-{[6-(1,8-二羟基蒽醌-3-甲酰氨基)己基]氨基}乙酰基-1,4,7,10-四氮杂环十二烷-1,4,7-三乙酸钆(Gd-DO3A-rhein)。采用大鼠再灌注肝坏死和肌肉坏死模型评价Gd-DO3A-rhein的坏死靶向性,分别在给予GdDO3A-rhein(0.1 mmol/kg)前和给药后0~12 h进行MRI成像,Gd-DOTA作为对照,成像结束后处死大鼠,对坏死组织进行HE和TTC染色验证坏死模型。MRI成像结果表明,在注射Gd-DO3A-rhein(0.1 mmol/kg)后3、12 h,坏死肝信号呈显著增强,坏死肝与正常肝对比度分别为1.61±0.14、2.36±0.20与给药前(1.16±0.10)呈显著性差异(P0.05),坏死肌肉呈现同样的结果。以上结果说明,该对比剂具有良好的坏死靶向性,具有成像坏死组织的潜力。
[Abstract]:Magnetic resonance imaging (MRI) contrast agent was synthesized using Rhein as substrate and its necrotic targeting was evaluated. A new ligand 10- {[6-HYDROXYLAXAQUINON-3-formylAMINO] HYDROXYL} AMINOXYL-1ONE 4710- Tetra was obtained by two-step acylation and two-step de-protection method. The heterocyclic nitrogen heterocyclic 12 alkane -1C 4C 4H 3A-rheinine was coordinated with Gd3 to obtain the paramagnetic contrast agent 10- {[6-O1O1-dihydroxyanthraquinone -3-formylamino] hexyl] acetyl -1-butadiol -44-tetraazacyclic 12 alkane -14-3-gadolinium acetate Gd-DO3A-rhein.Rat liver necrosis and liver necrosis were induced by reperfusion. Muscle necrosis model was used to evaluate the necrotic targeting of Gd-DO3A-rhein. MRI imaging of Gd-DOTA was performed before and 12 hours after administration of GdDO3A-rhein(0.1 mmol / kg, respectively. The rats were killed at the end of the imaging. The necrotic model was verified by HE and TTC staining. The results showed that the necrotic model was detected by HE and TTC staining. At 12 h after injection of Gd-DO3A-rhein(0.1 mmol / kg, the signal intensity of necrotic liver increased significantly. The contrast of necrotic liver and normal liver was 1.61 卤0.140.36 卤0.20 and 1.16 卤0.10, respectively. The contrast agent has good necrosis targeting and has the potential of imaging necrotic tissue.
【作者单位】：南京中医药大学第三临床医学院;江苏省中医药研究院转化医学实验室;中国药科大学天然药物化学教研室;
【基金】：国家自然科学基金资助项目(No.81473120) 常州四药医院药学科研基金资助项目(No.2014YX011)~~
【分类号】：R914

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