期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 64, 期 13, 页码 9182-9192出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.1c00393
关键词
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资金
- National Nature Science Foundation of China [81671675, 21172025, 81601490]
- Science and Technology Project of Municipal School Strategic Cooperation, Nanchong [NSMC20170100, 18SXHZ0091, 18SXHZ0379, NCKL201704]
The novel Mn-BnO-TyrEDTA contrast agent improves the accuracy of liver lesion detection in MRI through hepatocyte uptake and renal clearance pathways, and achieves hepatic targeting through the organic anion transporting polypeptides (OATPs) mediated amphiphilic anion contrast agent uptake.
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.
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