Baptiste TAFFOUREAU PhD defense
Design of hepatotropic peptide radiopharmaceuticals for targeting hepatocellular carcinoma: synthesis, radiolabeling and characterization
Friday 27 March, 13:30Passed
Organic Chemistry & Interfaces (COrInt) team
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, ranking sixth in incidence and third in mortality worldwide. The objective of this work was to develop novel drug candidates for the diagnosis and treatment of HCC. In previous studies, two hepatotropic peptides, GBVA10-9 and CPB, were identified as exhibiting strong tropism toward cancerous hepatic cells. The conjugation of these peptides to ligands, followed by their radiolabeling with diagnostic and/or therapeutic radionuclides, constituted an initial strategy for the management of HCC. However, despite pronounced hepatotropism observed in vitro, no significant tumor accumulation of the radiolabeled peptides was observed in vivo.
Based on these findings, the present work focused on optimizing these peptide vectors to improve their binding to tumor cells. To reach this goal, various linker with distinct physicochemical properties were inserted between the peptides and their ligands. The resulting peptide derivatives were radiolabeled with 68Ga and characterized in terms of their physicochemical properties and stability in human serum. Ten new derivatives were synthesized, radiolabeled, and analyzed, revealing linker-dependent differences in physicochemical properties and serum stability. These studies enabled the identification of new promising candidates for further biological investigations.
Jury
Pascal LOYER, Directeur de recherche, NuMeCan – INSERM / President
Thibault GENDRON, Chargé de cours, Université de Liège / Reviewer
Laurence MOINE, Directrice de recherche, Institut Galien Paris-Saclay - CNR / Reviewer
Isabelle QUELVEN-BERTIN, Maitre de conférences – Praticien hospitalier, ToNIC – INSERM / Examiner
Sandrine CAMMAS-MARION, Chargée de recherche, ISCR – CNRS / PhD Director
Mickaël BOURGEOIS, Professeur d’université – Praticien hospitalier, CRCI2NA – INSERM / PhD Co-Director
Nicolas LEPAREUR, Ingénieur Chercheur, Centre Eugène Marquis / PhD Co-Supervisor
Contact
Sandrine Cammas-Marion, sandrine.marion.1@ensc-rennes.fr, sandrine.marion@univ-rennes.fr
