坏死亲和性MRI对比剂Gd-DO3A-rhein的合成及其靶向性

卞丽; 高萌; 黄德健; 彭飞; 张健; 殷志琦

doi:10.11665/j.issn.1000-5048.20170305

坏死亲和性MRI对比剂Gd-DO3A-rhein的合成及其靶向性

卞丽¹,
高萌^1,2,
黄德健¹,
彭飞¹,
张健^1,2,
殷志琦³

1.
南京中医药大学第三临床医学院
2.
江苏省中医药研究院转化医学实验室
3.
中国药科大学天然药物化学教研室

基金项目: 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)

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- 刊出日期: 2017-06-24

Synthesis and necrosis target of necrosis-avid MRI contrast agent Gd-DO3A-rhein

摘要

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Gd-DO3A-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(P<0.05)，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。
- 大黄酸 /
- Gd-DO3A-rhein /
- 坏死靶向性 /
- 肝坏死 /
- 磁共振成像
Abstract: The purpose of this study was to synthesize and evaluate the necrosis target of MRI contrast agent based on rhein. The novel ligand 10-{［6-(1, 8-dihydroxyanthraquinone-3-carboxamido)hexyl］amino}acetyl-1, 4, 7, 10-tetraazacyclododecan-1, 4, 7-triacetic acid(DO3A-rhein)was synthesized by two-step acylation and two-step deprotection. The paramagnetic contrast agent gadolinium 10-{［6-(1, 8-dihydroxyanthraquinone-3-carboxamido)hexyl］amino} acetyl-1, 4, 7, 10-tetraazacyclododecan-1, 4, 7-triacetate(Gd-DO3A-rhein)was obtained by coordination of Gd³⁺ with the synthesized ligand. Its necrosis affinity was evaluated by liver infarction and muscular necrosis on rat models. The MRI was performed before administration of Gd-DO3A-rhein and during 0 h to 12 h after administration of Gd-DO3A-rhein(0. 1 mmol/kg), respectively, and Gd-DOTA was used as control. After MRI scanning, rats were sacrificed and necrotic tissues were stained using triphenyltetrazolium chloride(TTC)and hematoxylin-eosin(HE). MRI images of liver infarction and muscular necrosis on rat models showed significantly enhanced signal intensity compared with normal tissues. The contrast ratios of necrotic liver/normal liver were 1. 61±0. 14 and 2. 36±0. 20 at 3 h and 12 h postinjection of Gd-DO3A-rhein(0. 1 mmol/kg)respectively, demonstrating a significant difference compared with pre-administration of Gd-DO3A-rhein(1. 16±0. 10; P<0. 05). The same results were obtained from necrotic muscles. These findings suggested that Gd-DO3A-rhein possessed the necrosis target and imaging capability of necrotic tissues.
- rhein /
- Gd-DO3A-rhein /
- necrosis target /
- reperfused liver infarction /
- magnetic resonance imaging

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参考文献(17)

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坏死亲和性MRI对比剂Gd-DO3A-rhein的合成及其靶向性

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Synthesis and necrosis target of necrosis-avid MRI contrast agent Gd-DO3A-rhein

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