Synthesis and necrosis target of necrosis-avid MRI contrast agent Gd-DO3A-rhein / 中国药科大学学报

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.