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Evaluation de la radiothérapie vectorisée à l’aide de nanocapsules lipidiques chargées en rhénium-188 pour le traitement du glioblastome : investigation des modalités d’administrations locales

Abstract : High grade glial brain tumors are defined as glioblastomas. Nowadays, they are incurable. The current therapeutic purposal (surgical resection, external radiotherapy and chemotherapy) doesn’t extend the patients median survival time up to a few months. Newstrategies as nanomedicines loaded with a radionuclide( or  emitter) have been evaluated in clinical trials. As tate of the art of this domain’s technologies is described in a first part which analyses the important criteria to take account in vectorized radiotherapy like the radionuclides, the route of administration and the vectors used. Then, it is concluded with a presentation of preclinical on going studies as the use of nanovectors loaded with a radioisotope : the LNC188Re-SSS. The second part illustrates the therapeutical strategy application on a xenograft mice model. The data showan eradication of the tumor mass of treated mice withthe personalized convection-enhanced delivery offractionated radiotherapy. Furthermore, it describes the LNC distribution and the direct radiation effects on tumor cells (atypical giant cells, polyploïdy) supported by an inflammatory infiltration (innate immune effectors). An evaluation on the GL261 mice model has been realized and concerns the third part of this thesis. In perspectives, the transfer of these data to clinical trials could be facilitated thanks to the dog spontaneous glioma model. This tumor share characteristics with the human neoplasma. Finally, this work will aim to validate the automated intracranial injection procedures.
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Annabelle Cikankowitz. Evaluation de la radiothérapie vectorisée à l’aide de nanocapsules lipidiques chargées en rhénium-188 pour le traitement du glioblastome : investigation des modalités d’administrations locales. Médecine humaine et pathologie. Université d'Angers, 2015. Français. ⟨NNT : 2015ANGE0057⟩. ⟨tel-02082316⟩

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