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AbstractAbstract
[en] This PhD work aimed at developing new bispidine-based copper(II) chelating agents for applications in Positron Emission Tomography (PET). On one hand, 64Cu is a metallic radioisotope which possesses interesting properties for PET imaging and on the other hand, bispidines have a pre-organized and rigid structure. This property makes them good chelating agents for numerous transition metals, particularly copper(II). This work presents the development of a new bispidine-based ligand having a phosphonate pendant arm as well as the development of bispidines allowing the synthesis of new chelating agents for copper(II). The physico-chemical properties of the phosphonated bispidine were thoroughly studied by different techniques, showing that it would be adequate for PET applications. Radiolabeling experiments were also done in the presence of 64Cu for various bispidines and show the high potential of bispidine ligands for the complexation of 64Cu. Finally, several functionalization strategies were studied in order to get bifunctional chelates based on the phosphonated bispidines. This study proved the possibility to develop two bifunctional bispidines based on the phosphonated one and also it allowed us to develop two bifunctional bispidines as synthon for the synthesis of new families of bifunctional bispidines. (author)
[fr]
Ce travail de these avait pour objectif de developper de nouveaux chelatants du cuivre(II) de type bispidine pour des applications en Tomographie a Emission de Positrons. Le 64Cu est un radioisotope metallique dont les proprietes sont interessantes pour la TEP. Les bispidines sont des chelatants dont la structure est preorganisee et rigide. Cette propriete confere au bispidine de bonnes proprietes de coordination vis-a-vis des metaux de transition, en particulier le cuivre(II). Ce travail presente le developpement d'un ligand de type bispidine possedant un groupement phosphonate ainsi que le developpement de bispidines permettant la synthese de nouvelles familles de chelatants pour le cuivre(II). La bispidine phosphonatee a ensuite fait l'objet d'une etude physico-chimique par differentes techniques, revelant ainsi qu'elle possede les caracteristiques requises pour des applications en TEP. Le radiomarquage en presence de 64Cu a ete etudie pour une selection de plusieurs chelatants et montre le fort potentiel des ligands de type bispidine pour la complexation du 64Cu. Enfin, diverses strategies de fonctionnalisation ont ete etudiees pour l'obtention d'un chelatant bifonctionnel base sur la bispidine phosphonatee. Ces strategies demontrent la possibilite d'obtenir deux ligands bifonctionnels. De surcroit, deux plateformes bifonctionnelles peuvent faire l'objet de point de depart pour le developpement de nouvelles familles de bispidines bifonctionnelles. (auteur)Original Title
Synthese et caracterisation de bispidines, chelatants du 64Cu, en vue d'applications pour la tomographie a emission de positrons
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Source
13 Oct 2017; 292 p; 253 refs.; Available from the INIS Liaison Officer for France, see the INIS website for current contact and E-mail addresses; These Docteur de l'universite de Strasbourg, Discipline: Chimie
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Miscellaneous
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Thesis/Dissertation
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BETA DECAY RADIOISOTOPES, BETA-MINUS DECAY RADIOISOTOPES, BETA-PLUS DECAY RADIOISOTOPES, CHEMICAL ANALYSIS, COMPUTERIZED TOMOGRAPHY, COPPER ISOTOPES, DIAGNOSTIC TECHNIQUES, ELECTRON CAPTURE RADIOISOTOPES, EMISSION COMPUTED TOMOGRAPHY, GALLIUM ISOTOPES, HOURS LIVING RADIOISOTOPES, INTERMEDIATE MASS NUCLEI, ISOTOPES, NUCLEI, ODD-ODD NUCLEI, ORGANIC COMPOUNDS, ORGANIC PHOSPHORUS COMPOUNDS, QUANTITATIVE CHEMICAL ANALYSIS, RADIOISOTOPES, SPECTRA, TITRATION, TOMOGRAPHY, VOLUMETRIC ANALYSIS
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