Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Chengdu 610041, China.
J Med Chem. 2021 Jul 8;64(13):9182-9192. doi: 10.1021/acs.jmedchem.1c00393. Epub 2021 Jun 21.
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.
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。