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Title: Uniquely branched and structurally versatile lanthanide-based contrast agents for MRI
Author: Balali-Mood, Beeta
ISNI:       0000 0004 2715 9898
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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This thesis focuses on the development of sensitive, yet kinetically stable, (i.e. non-toxic) contrast agents for Magnetic Resonance Imaging (MRI). MRI is a widely used medical imaging technique in both research and clinical contexts. While currently approved contrast agents have significantly contributed to advancement of clinical diagnosis, there is an increasing need for development of contrast agents with high relaxivity (‘MRI activity’). This demand is approached in the current project by using a tetra-alkynyl cyclen-based ligand to: a. Work towards formation of a gadolinium-based ‘cage’ which would entrap the Gd centre within its cavity in a less coordinatively saturated manner than the current Gd-based MRI contrast agents. b. Synthesize novel oligomeric gadolinium-chelates with improved relaxivity profiles. Two families of oligomeric lanthanide-chelates were synthesized via Huisgen 1,3-dipolar and Diels Alder cycloadditions. The oligomers were produced with A4/B2 hyperbranched polymerisation methodology. The relaxation enhancement properties of the oligomeric Gd(III) and luminescence and where possible Paramagnetic Chemical Exchange Saturation Transfer (ParaCEST) profiles of the oligomeric Eu(III) chelates were studied. The relaxivity studies showed up to a four-fold increase in relaxivity as compared to their corresponding monomer. This is the first example of such significant enhancement in relaxivity of a tetrakis (acetamido)- 1,4,7,10-tetraazacyclododecane (DOTAM)-based gadolinium containing agent. The branched polymers presented in this work, can be modified such that further functional groups can be incorporated with stoichiometric control bearing targeted moieties to image specific biological events. To this end, work was carried towards development of a two different designs for pyridyl-based phosphate-sensing Ln-based complex.
Supervisor: Steinke, Joachim ; Vilar Compte, Ramon Sponsor: EPSRC ; Imperial College Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral