Manganese (II) Complex of 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid (NOTA) as a Hepatobiliary MRI Contrast Agent

被引：9

作者：

Islam, Md. Kamrul ^{[1
]}

Baek, Ah-Rum ^{[1
]}

Yang, Byeong-Woo ^{[2
]}

Kim, Soyeon ^{[3
]}

Hwang, Dong Wook ^{[4
]}

Nam, Sung-Wook ^{[4
]}

Lee, Gang-Ho ^{[5
]}

Chang, Yongmin ^{[2
,4
,6
]}

机构：

[1] Kyungpook Natl Univ, Inst Biomed Engn Res, Daegu 41405, South Korea

[2] Kyungpook Natl Univ, Sch Med, Dept Med & Biol Engn, Daegu 41944, South Korea

[3] Korea Inst Radiol & Med Sci, Div RI Convergence Res, Seoul 01812, South Korea

[4] Kyungpook Natl Univ, Sch Med, Dept Mol Med, Daegu 41944, South Korea

[5] Kyungpook Natl Univ, Dept Chem, 80,Daehak Ro, Daegu 41566, South Korea

[6] Kyungpook Natl Univ Hosp, Dept Radiol, Daegu 41944, South Korea

来源：

PHARMACEUTICALS | 2023年 / 16卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

magnetic resonance imaging; manganese; contrast agent; naphthalene; liver imaging; GD-EOB-DTPA; GADOLINIUM; ENHANCEMENT; TRANSPORTERS; REPLACEMENT; CONJUGATE; STABILITY; FIBROSIS; PROTEIN;

D O I：

10.3390/ph16040602

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Magnetic resonance imaging (MRI) is increasingly used to diagnose focal and diffuse liver disorders. Despite their enhanced efficacy, liver-targeted gadolinium-based contrast agents (GBCAs) raise safety concerns owing to the release of toxic Gd3+ ions. A pi-conjugated macrocyclic chelate, Mn-NOTA-NP, was designed and synthesized as a non-gadolinium alternative for liver-specific MRI. Mn-NOTA-NP exhibits an r(1) relaxivity of 3.57 mM(-1) s(-1) in water and 9.01 mM(-1) s(-1) in saline containing human serum albumin at 3 T, which is significantly greater than the clinically utilized Mn2+-based hepatobiliary drug, Mn-DPDP (1.50 mM(-1) s(-1)), and comparable with that of GBCAs. Furthermore, the in vivo biodistribution and MRI enhancement patterns of Mn-NOTA-NP were similar to those of the Gd3+-based hepatobiliary agent, Gd-DTPA-EOB. Additionally, a 0.05 mmol/kg dose of Mn-NOTA-NP facilitated high-sensitivity tumor detection with tumor signal enhancement in a liver tumor model. Ligand-docking simulations further indicated that Mn-NOTA-NP differed from other hepatobiliary agents in their interactions with several transporter systems. Collectively, we demonstrated that Mn-NOTA-NP could be a new liver-specific MRI contrast agent.

引用

页数：17