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

The purpose of this study is to assess the physicochemical propertiesand 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 anasymmetric alpha-substituted pendant arm as potential hepatocyte-specific magneticresonance imaging contrast agents (MRI CAs). Ourfindings show thatfineconformational changes in the chelating arm affect thein vivopharmacokineticbehavior of the MRI CA, and that a six-membered chelating substituent of Gd-SucL ismore advantageous in this system to avoid unwanted interactions with endogenousspecies. Gd-SucL exhibited a general DOTA-like chelate stability trend, indicating thatall chelating arms retain coordination bonding. Finally, thein vivodiagnostic efficacy ofhighly stable Gd-SucL as a potential hepatocyte-specific MRI CA was evaluated usingT1-weighted MR imaging on an orthotopic hepatocarcinoma model.