Lipophilic Group-Modified Manganese(II)-Based Contrast Agents for Vascular and Hepatobiliary Magnetic Resonance Imaging
Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
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| Enthalten in: |
Journal of medicinal chemistry - 67(2024), 6 vom: 28. März, Seite 5011-5031 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cai, Zhongyuan [VerfasserIn] |
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| Links: |
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| Themen: |
42Z2K6ZL8P |
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| Anmerkungen: |
Date Completed 29.03.2024 Date Revised 29.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.jmedchem.4c00120 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369403916 |
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| 520 | |a Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides | ||
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| 700 | 1 | |a Cao, Yingzi |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Shengxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shasha |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yuting |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Haojie |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Xiaomin |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Shimin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Jiang |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Weidong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Zhuzhong |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Chunchao |e verfasserin |4 aut | |
| 700 | 1 | |a Lui, Su |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Qiyong |e verfasserin |4 aut | |
| 700 | 1 | |a Ai, Hua |e verfasserin |4 aut | |
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