Radiomarquage au 99mTc des IgA et IgG : optimisation du marquage, étude in vitro, biodistribution chez l'animal sain et sur modèle tumoral

Abstract : Since their discovery in 1975, by Köhler and Milstein, monoclonal antibodies (mAbs) world has significantly evolved and they currently hold a prominent place in cancers care. Today, the mAbs, having a marketing authorization or in clinical trial, are all IgG class (IgG1). However, this Ab class showed limitations on its use, and the study of other isotypes, such as IgA, could be interesting. Unlike IgG, IgA, original isotype particularly because of their heterogeneity in molecular forms, remains understudied. In this work, we propose a radiolabeling of monomeric, polymeric and secretory IgA with 99mTc by an indirect method, involving 2-iminothiolane and tricarbonyl core. Biodistribution of radiolabeled monomeric and polymeric IgA was evaluated, after intravenous administration, in healthy animals and in mucosal tumor-bearing animals. These studies have allowed us to glimpse the IgA diagnostic potential, but also their interest in targeted therapy of tumors with mucosal localization. Moreover, thanks to their enzymatic strength and retranscytosis, a new administration route of mAbs could be developed. In this context, secretory IgA were administered orally in preliminary biodistribution studies.
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Hélène Carpenet Guéry. Radiomarquage au 99mTc des IgA et IgG : optimisation du marquage, étude in vitro, biodistribution chez l'animal sain et sur modèle tumoral. Médecine humaine et pathologie. Université de Limoges, 2015. Français. ⟨NNT : 2015LIMO0074⟩. ⟨tel-01423871⟩

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