Développement de nouvelles méthodes de marquage au fluor-18 pour peptides et oligonucléotides en vue de leur études par tomographie par émission de positons
[en] Positron Emission Tomography is a highly sensitive imaging technique currently available in nuclear medicine for diagnostic. In regard to his physical and nuclear characteristics, fluorine-18 appears often as the radionuclide of choice for the preparation of short-lived positron-emitter radiotracers for PET studies. The fluorine-18 labelling reaction for biomolecules requires very mild conditions. The current method for highly efficient fluorine-18 labelling of biomolecules is the conjugation of a [18F]prosthetic group with a reactive function on the organic compound. During this thesis, two techniques were developed to label biomolecules via a [18F]prosthetic group: the first one to label tyrosine-containing peptides and the second one to label a siRNA. The first part of this work present the synthesis of the [18F]F-PTAD which is a agent for specific radiolabelling of tyrosine. [18F]F-PTAD was coupled with a tyrosine with a global radiochemical yield (synthesis, coupling, purification) of 20% (DC) and the synthesis lasts 2h30. During the second part of this work, two alkyne-bearing linkers were synthesized. These linkers were ligated with siRNA and then reacted with azide-bearing [18F]prosthetic group via a Huisgen cycloaddition reaction. The [18F]siRNA is then obtained with an global radiochemical yield of 12% (DC) and the synthesis lasts 2h00. In conclusion, two methods for labeling biomolecules have been developed.
Disciplines :
Chemistry
Author, co-author :
Flagothier, Jessica ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de chimie organique de synthèse
Language :
French
Title :
Développement de nouvelles méthodes de marquage au fluor-18 pour peptides et oligonucléotides en vue de leur études par tomographie par émission de positons
Alternative titles :
[en] New 18F-radioloabelling methods of peptides and oligonucleotides for positrons emission tomography studies
Defense date :
09 September 2014
Number of pages :
170
Institution :
ULiège - Université de Liège
Degree :
Docteur en Sciences
Promotor :
Luxen, André ; Université de Liège - ULiège > Département de chimie (sciences)
President :
Quinton, Loïc ; Université de Liège - ULiège > Molecular Systems (MolSys)
Jury member :
Lemaire, Christian ; Université de Liège - ULiège > GIGA > GIGA CRC In vivo Imaging - Radiochemistry
Mievis, Frédéric ; Université de Liège - ULiège > Unités de recherche interfacultaires > GIGA-CRC In vivo Imaging (Centre de Recherche du Cyclotron)