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Etude des générateurs in vivo Pb-212/Bi-212 et U-230/Th-226 pour la radiothérapie alpha ciblée

Alicia Le Du 1
1 radiochimie
SUBATECH - Laboratoire SUBATECH Nantes
Abstract : Alpha-radioimmunotherapy is a promising cancer therapy that uses a-particles vectorized by monoclonal antibody to break down cancerous tumors. The notion of in vivo generator was introduced in 1989 by Leonard Mausner. The concept involves labeling of various molecular carriers (antibodies, peptides, etc) with intermediate half-life generator parents, which after accumulation in the desired tissue generate much shorter half-life daughter radionuclide. This thesis focuses on the study of two in vivo generators potentially interesting for alpha-radioimmunotherapy: Pb-212 / Bi-212 generator and U-230 / Th-226 generator. The first part of this work presents the Pb-212 / Bi-212 generator, two approaches allowing the vectorisation. Chelation approach on a protein and an approach by encapsulation in liposomes have been proposed. This last approach appears to be the most interesting. In vitro stability studies have been performed on these labeling. The second part of this work presents the U-230 / Th-226 generator. Studies have first been made to achieve a theoretical model to describe the speciation of Th(IV) in human serum. The efficacy of DTPA as chelating agent for complexation of Th(IV) in human serum could thus be estimated.
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Alicia Le Du. Etude des générateurs in vivo Pb-212/Bi-212 et U-230/Th-226 pour la radiothérapie alpha ciblée. Radiochimie. Université de Nantes, 2011. Français. ⟨tel-00779481⟩

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