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

摘要

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.