Development and characterization of new metal-based nanosystems as diagnostic probes for molecular imaging

Gd(III)-based MRI contrast agents are widely used, but are nowadays raising concerns about safety and their environmental impact. To overcome these issues, research is focusing on two main strategies: (1) replacing Gd(III) with alternative metals like Mn(II) and Fe(III), which offer lower toxicity and favorable properties, and (2) developing nanoparticles to enhance relaxivity by increasing local probe concentration and reducing rotational dynamics. This work investigates both approaches, developing nanoparticles with Gd(III), Dy(III), Mn(II), and Fe(III), focusing on their coordination chemistry and MRI efficiency. Three main sections structure the study: Paramagnetic Nanogels – Ionic and covalent nanogels incorporating various metal chelates were studied to understand their hydration and water interactions. Coordination Polymers – Fe(III)-gallic acid polymers with different coatings were examined, highlighting how hydrophilicity enhances relaxivity via second-sphere interactions. T₁ and T₂ Characterization – A novel method was developed to determine water exchange rates without requiring high ¹⁷O-NMR concentrations. Applied to Ln(III)-DTPA and -AAZTA systems, it successfully determined kex. This method was further tested on a Dy(III)-nanogel, revealing key relaxivity determinants. This study advances MRI contrast agent design by optimizing relaxivity and exploring safer, effective alternatives to Gd(III).