Publication： Journal of Medicinal Chemistry

Date of Publication: April 14, 2022

Authors： 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, and Yongmin Chang

DOI: https://doi.org/10.1021/acs.jmedchem.2c00291

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.