Synthèse de nouveaux agents bimodaux hydrosolubles pour l'IRM, l'imagerie nucléaire, l'imagerie biphotonique et la génération de second harmonique

摘要

The goal of my PhD studies was to synthesize new compounds for possible medical imaging applications. The first part of my thesis focused on the synthesis of heteroleptic ligands to achieve the chelation of two different metals aimed at addressing two types of medical imaging. We first synthesized porphyrins, which are well-known for the chelation of numerous transition metals. We focused on copper, whose copper-64 isotope is a β+ emitter usable in Positron Emission Tomography (PET). These porphyrins have been coupled with a DOTA derivative. This molecule, metallated with gadolinium, is well-known in Magnetic Resonance Imaging (MRI). Our compounds display encouraging relaxivities for MRI applications. At last, these molecular probes have been conjugated to a few biomolecules in order to vectorize our compounds. The second part of this work is related to the synthesis of fluorophores for nonlinear optical imaging. We first synthesized amphiphilic zwitterionic porphyrins for Second Harmonic Generation (SHG). The efficiency of these compounds has been measured and was satisying enough to consider the possibility to perform imaging studies. We also worked on the synthesis of compounds for Two Photon Emission Fluorescence (TPEF) imaging and MRI. We have linked a DOTA derivative with a diketopyrrolopyrrole (DPP). This conjugate has been metallated with gadolinium and its relaxivity has been measured. Interestingly, this value is superior to that of DOTA(Gd).