Synthesis and evaluation of necrosis avidity of MRI contrast agent Gd-DO3A-Ether-Rhein
10.11665/j.issn.1000-5048.20190409
- VernacularTitle:MRI对比剂Gd-DO3A-Ether-Rhein的合成及其坏死亲和性研究
- Author:
Libang ZHANG
1
,
2
;
Dongjian ZHANG
;
Meng GAO
;
Qiaomei JIN
;
Tianze WU
;
Yang YANG
;
Jian ZHANG
;
Zhiqi YIN
Author Information
1. 中国药科大学中药学院中药制剂系&
2. 天然药物活性组分与药效国家重点实验室；江苏省中医药研究院转化医学实验室；南京中医药大学附属中西医结合医院 南京 210028
- Publication Type:Journal Article
- Keywords:
rhein;
Gd-DO3A-Ether-Rhein;
necrosis avidity;
contrast agent;
magnetic resonance imaging
- From:
Journal of China Pharmaceutical University
2019;50(4):444-451
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study was to synthesize and evaluate the necrosis avidity of MRI contrast agent based on rhein and linked by ether. The novel ligand 10-{［6-(1, 8-dihydroxyanthraquinone-3-carboxamido)ethoxyethyl］amino}carbonylmethyl-1, 4, 7, 10-tetraazacyclododecan-1, 4, 7-triacetic acid(DO3A-Ether-Rhein, E1)was synthesized by two steps of acylation and deprotection reaction. The paramagnetic gadolinium 10-{［6-(1, 8-dihydroxyanthraquinone-3-carboxamido)ethoxyethyl］amino}carbonylmethyl-1, 4, 7, 10-tetraazacyclododecan-1, 4, 7-triacetic acid(Gd-DO3A-Ether-Rhein, GdE1)was obtained by coordination of Gd3+ with the above ligand. We examined the necrotic avidity of GdE1 in human hepatocellular carcinoma HepG2 cell necrosis induced by hyperthermia in vitro and in rat model with muscular necrosis induced by microwave ablation in vivo by MRI. The MRI was implemented before administration of GdE1 and during 0-9 h after administration of GdE1(0. 1 mmol/kg), and Gd-DOTA(gadolinium 1, 4, 7, 10-tetraacetic acid-1, 4, 7, 10-tetraazacyclo dodecane)was used as control. The signal intensity of necrotic cells(4 369±70)was significantly higher than that of normal cells(2 555±84)(P< 0. 05). Similarly, the contrast ratio between necrotic and normal muscle at 3 h after administration of GdE1(2. 00±0. 12)was remarkblely higher than that at 0 h after administration of GdE1(1. 27±0. 03)(P< 0. 05). Therefore, GdE1 presents good necrosis affinity and has the potential to be used in the diagnosis of necrosis-related diseases.
