Development of radiolabelling with fluoride-18 of fluoro-aminoesters via aziridinium intermediate and radiosynthesis of [¹¹C]sulfasalazine for PET imaging

Aminoacid transporters are often overexpressed in tumour cells and represent a favoured molecular target for Positron Emitted Tomography (PET) imaging of cancers. In order to access to specific radiotracers of this transporters, this thesis works consisted of development of - in a first part, a new radiolabeling method with fluorine-18 of fluoro-aminoacids based on deoxy-radiofluorination of hydroxyamino-ester precursors via an aziridinium intermediate - and in a second part, radiolabelling with carbon-11 of sulfasalazine, an selective inhibitor of Xc- transporters. Deoxy-radiofluorination reaction from serine, methylserine or hydroxyphenylalanine hydroxy-aminoesters, stable and easily accessible precursors, allowed effectible and reproducible formation of [¹⁸F]fluoro-aminoesters at room temperature. Regioselectivity was influenced by substituents of aziridinium ring and amine. Radiosynthesis of [¹¹C]sulfasalazine has been successfully realised by coupling reaction between diazonium salt and [¹¹C]salicylic acid, obtained by [¹¹C]carboxylation of bis-magnesium precursor from iodophenol. Automated radiosynthesis is in progress to produce [¹¹C]sulfasalazine with sufficient quantity to in vivo studies. (author)