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

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.