Islam Md Kamrul, Kim Soyeon, Kim Hee-Kyung, Park Subin, Lee Gang-Ho, Kang Hyo Jeung, Jung Jae-Chang, Park Joon-Suk, Kim Tae-Jeong, Chang Yongmin
Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation , Chumbok-ro 80, Dong-gu, Daegu 41061, Korea.
J Med Chem. 2017 Apr 13;60(7):2993-3001. doi: 10.1021/acs.jmedchem.6b01799. Epub 2017 Mar 22.
A novel manganese(II) complex based on an ethylenediaminetetraacetic acid (EDTA) coordination cage bearing a benzothiazole aniline (BTA) moiety (Mn-EDTA-BTA) was designed and synthesized for use as a liver-specific MRI contrast agent with high chelation stability. In addition to forming a hydrophilic, stable complex with Mn, this new Mn chelate was rapidly taken up by liver hepatocytes and excreted by the kidneys and biliary system. The kinetic inertness and R relaxivity of the complex were much higher than those of mangafodipir trisodium (MnDPDP), a clinically approved liver-specific MRI contrast agent. The diagnostic utility of this new Mn complex in MRI was demonstrated by high-sensitivity tumor detection in an animal model of liver cancer.
设计并合成了一种基于带有苯并噻唑苯胺(BTA)部分的乙二胺四乙酸(EDTA)配位笼的新型锰(II)配合物(Mn-EDTA-BTA),用作具有高螯合稳定性的肝脏特异性MRI造影剂。除了与锰形成亲水性稳定配合物外,这种新型锰螯合物还能被肝脏肝细胞迅速摄取,并通过肾脏和胆道系统排泄。该配合物的动力学惰性和弛豫率比临床批准的肝脏特异性MRI造影剂锰福地匹三钠(MnDPDP)高得多。在肝癌动物模型中通过高灵敏度肿瘤检测证明了这种新型锰配合物在MRI中的诊断效用。