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Effect of Structural Fine-Tuning on Chelate Stability and Liver Uptake of Anionic MRI Contrast Agents

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posted on 2022-04-14, 08:05 authored by Ah Rum Baek, Hee-Kyung Kim, Soyeon Kim, Ji-ung Yang, Min-Kyoung Kang, Jae Jun Lee, Bokyung Sung, Hyeji Lee, Minsup Kim, Art E. Cho, Ji-Ae Park, Yongmin Chang
The purpose of this study is to assess the physicochemical properties and MRI diagnostic efficacy of two newly synthesized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-type Gd chelates, Gd-SucL and Gd-GluL, with an asymmetric α-substituted pendant arm as potential hepatocyte-specific magnetic resonance imaging contrast agents (MRI CAs). Our findings show that fine conformational changes in the chelating arm affect the in vivo pharmaco­kinetic behavior of the MRI CA, and that a six-membered chelating substituent of Gd-SucL is more advantageous in this system to avoid unwanted interactions with endogenous species. Gd-SucL exhibited a general DOTA-like chelate stability trend, indicating that all chelating arms retain coordination bonding. Finally, the in vivo diagnostic efficacy of highly stable Gd-SucL as a potential hepatocyte-specific MRI CA was evaluated using T1-weighted MR imaging on an orthotopic hepato­carcinoma model.

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