Chitosan‐Based Nanogels Containing Ln³⁺ Chelates (Ln=Gd, Dy) as T₁ and T₂ MRI Probes

Abstract

Novel nanogels, characterized by high stability and incorporating macrocyclic chelates of Gd(III) and Dy(III), were synthesized and assessed for their effectiveness as T1 and T2 relaxation agents, respectively. In this specific design, we employed octacoordinated bifunctional Gd‐1,7‐DOTAGA2 chelate to cross‐link chitosan chains. The results revealed that the sample exhibited a relaxivity value at clinical magnetic field strengths (1.5 T), approximately seven times higher than that of currently available clinical contrast agents and good MRI contrast efficacy at both 7.1 and 1 T. Furthermore, the nanogel displayed excellent stability in biological fluids, with no discernible interactions with serum biomolecules and no release of metal. In addition to Gd(III)‐based probes commonly used as T1 positive contrast agents, the nanogel with the corresponding Dy‐1,7‐DOTAGA2 chelate was prepared to explore its potential as a T2 MRI probe. Dy‐based nanogel demonstrated notably elevated transverse relaxivity values compared to the free chelate at high magnetic fields (> 3 T) and significant T2 MRI contrast at 7.1 T, a capability often lacking when employing an equivalent concentration of a low‐molecular‐weight Dy(III) complex. The characterization of paramagnetic complexes was completed through the measurement of 1H NMRD profiles and 17O NMR data.