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亲脂基团修饰乙二胺四乙酸(EDTA)的 Mn(II) 配合物作为新型肝胆磁共振成像对比剂。

Mn(II) Complex of Lipophilic Group-Modified Ethylenediaminetetraacetic Acid (EDTA) as a New Hepatobiliary MRI Contrast Agent.

机构信息

Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Chengdu 610041, China.

出版信息

J Med Chem. 2021 Jul 8;64(13):9182-9192. doi: 10.1021/acs.jmedchem.1c00393. Epub 2021 Jun 21.

Abstract

Liver-specific contrast agents (CAs) can improve the Magnetic resonance imaging (MRI) detection of focal and diffuse liver lesions by increasing the lesion-to-liver contrast. A novel Mn(II) complex, Mn-BnO-TyrEDTA, with a lipophilic group-modified ethylenediaminetetraacetic acid (EDTA) structure as a ligand to regulate its behavior in vivo, is superior to Gd-EOB-DTPA in terms of a liver-specific MRI contrast agent. An MRI study on mice demonstrated that Mn-BnO-TyrEDTA can be rapidly taken up by hepatocytes with a combination of hepatobiliary and renal clearance pathways. Bromosulfophthalein (BSP) inhibition imaging, biodistribution, and cellular uptake studies confirmed that the mechanism of hepatic targeting of Mn-BnO-TyrEDTA is the hepatic uptake of the amphiphilic anion contrast agent mediated by organic anion transporting polypeptides (OATPs) expressed by functional hepatocytes.

摘要

肝脏特异性对比剂 (CAs) 可以通过增加病变与肝脏的对比来提高磁共振成像 (MRI) 对局灶性和弥漫性肝脏病变的检测。一种新型的 Mn(II) 配合物 Mn-BnO-TyrEDTA,具有疏水性基团修饰的乙二胺四乙酸 (EDTA) 结构作为配体,以调节其在体内的行为,在肝脏特异性 MRI 对比剂方面优于 Gd-EOB-DTPA。一项关于小鼠的 MRI 研究表明,Mn-BnO-TyrEDTA 可以通过肝胆和肾脏清除途径的组合被迅速摄取到肝细胞中。溴磺酞 (BSP) 抑制成像、生物分布和细胞摄取研究证实,Mn-BnO-TyrEDTA 肝靶向的机制是通过功能肝细胞表达的有机阴离子转运蛋白 (OATPs) 介导的亲脂性阴离子对比剂的肝摄取。

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