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

BIAN Li; GAO Meng; HUANG Dejian; PENG Fei; ZHANG Jian; YIN Zhiqi

doi:10.11665/j.issn.1000-5048.20170305

Journal of China Pharmaceutical University > 2017 > 48(3): 282-288. > DOI: 10.11665/j.issn.1000-5048.20170305

BIAN Li, GAO Meng, HUANG Dejian, PENG Fei, ZHANG Jian, YIN Zhiqi. Synthesis and necrosis target of necrosis-avid MRI contrast agent Gd-DO3A-rhein[J]. Journal of China Pharmaceutical University, 2017, 48(3): 282-288. DOI: 10.11665/j.issn.1000-5048.20170305

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

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

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