Innovative smart probes for molecular imaging applications

Abstract

The main purpose of the present doctoral thesis is the development of new systems based on metal complexes for their application as contrast agents in Magnetic Resonance Imaging (MRI). To achieve this aim, this study encompasses the design, synthesis and characterisation of new metal complexes of the lanthanide ions or transition metal ions (Mn2+ or Ni2+), as well as a detailed investigation of their structures and physicochemical properties, both in solution and in the solid state. In addition, in vitro studies have also been carried out to assess their potential as contrast agents in MRI applications. Theoretical studies were performed using density functional theory (DFT) providing structural information of the complexes in solution, as well as information at the molecular level on the mechanisms that provide MRI response. The complexes presented in this work provide response at different frequencies (1H or 19F), either following the classical mechanism of longitudinal relaxation enhancement (Mn2+, Gd3+), or through the chemical exchange saturation transfer mechanism. This project was executed within the framework of the European COST Action CA15209 ("European Network on NMR Relaxometry"), funded by the European Science Foundation. Furthermore, it has been funded by the Research Projects “New Generation of Contrast Agents for Magnetic Resonance Imaging (MRI) Alternative to Gadolinium Derivatives” (CTQ2016-76756-P), “Innovative Smart Probes for Molecular Imaging Applications” (CTQ2013-43243-P) and the grant for predoctoral contracts for doctoral training associated to this Project (FPI grant, BES-2014-068399), funded by the Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness). The results achieved during this project lays the foundations for providing new products for medical application with competitive advantages over the current state-of-art.