Synthesis, Stability, and Relaxivity Measurement of Gd (III) Complexes of DOTA Ligands Derived from Amino Acids

To enhance the efficacy of magnetic resonance imaging (MRI), numerous novel contrast agents have been developed, with peptide modification emerging as a promising strategy. The versatility of peptides renders them particularly useful molecules for the fabrication of new molecule. However, the influence of peptide side chain modification on the imaging performance of contrast agents has not been fully explored in existing studies. Herein, we employed XK (ε-DOTA-Gd) X as a Gd-DOTA-peptide template and the X molecule underwent amino acid block substitution. Six Gd-DOTA-peptide complexes were synthesized and their properties, such as relaxivity, biostability, and biocompatibility, were measured and in vitro MRI assays were carried out. The results demonstrated that the Gd-DOTA-peptides exhibited low hemolysis rates and cytotoxicity. In plasma, the half-lives of the Gd-DOTA-peptide contrast agents exceeded 5 h. Relaxation experiments revealed that the Gd-DOTA-peptide achieved a slightly higher relaxation rate compared with the commercial agent Dotarem. Therefore, the amino acid modularize modification on the gadolinium-based MRI contrast agents were effective and worthy of further investigation.