Towards novel polymeric contrast agents for magnetic resonance imaging
File(s)
Author(s)
Martinelli, Jonathan
Type
Thesis
Abstract
This project centres on the exploration of novel contrast agents for Magnetic Resonance Imaging, with improved performances to signal specific objects in high- resolved images of the human body for medical and diagnostic purposes, and in particular for labelling and tracking stem cells after transplantation. The target agents are based on polymeric molecular architectures containing several MRI probes, thus being able to solve the sensitivity problems commonly known to affect this technique. The molecular structure was also designed to prevent those factors known to affect and limit the performances of contrast agents previously reported in the literature.
Following a thorough literature research, complexes of gadolinium(III) were chosen, in particular with l,4,7,10-tetraazacyclododecane-l,4,7,l0-tetraacetic acid (DOTA) as macrocyclic ligand due to its known ability to form highly stable (i.e. nontoxic) complexes. Furthermore, this ligand opens up the possibility for its modification and functionalisation in order to obtain a final molecular structure with desired well- defined properties.
The synthetic strategy was then planned and carried out, leading first to compounds which represent intermediate structures needed for further development. Most of them are themselves new substances not reported before.
The corresponding gadolinium(III)-complexes of some intermediates were prepared and tested on cell cultures for an evaluation of their biocompatibility and performances as contrast agents.
The prepared monomers were then used in several attempts of polymerisation exploiting different principles and techniques (radical, metathesis, “click-chemistry”); when successful, such procedures led to products which were characterised by suitable analytical methods, and eventually tested as contrast agents for MRI in terms of their relaxation performances and biological safety.
Following a thorough literature research, complexes of gadolinium(III) were chosen, in particular with l,4,7,10-tetraazacyclododecane-l,4,7,l0-tetraacetic acid (DOTA) as macrocyclic ligand due to its known ability to form highly stable (i.e. nontoxic) complexes. Furthermore, this ligand opens up the possibility for its modification and functionalisation in order to obtain a final molecular structure with desired well- defined properties.
The synthetic strategy was then planned and carried out, leading first to compounds which represent intermediate structures needed for further development. Most of them are themselves new substances not reported before.
The corresponding gadolinium(III)-complexes of some intermediates were prepared and tested on cell cultures for an evaluation of their biocompatibility and performances as contrast agents.
The prepared monomers were then used in several attempts of polymerisation exploiting different principles and techniques (radical, metathesis, “click-chemistry”); when successful, such procedures led to products which were characterised by suitable analytical methods, and eventually tested as contrast agents for MRI in terms of their relaxation performances and biological safety.
Date Issued
2009
Date Awarded
2009
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
Steinke, Dr. Joachim H. G.
Vilar, Dr. Ramon
Ferretti, Dr. Patrizia
Publisher Department
Department of Chemistry.
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)