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Les nanocapsules lipidiques chargées en Rhénium-188 : nouvel outil pour la radiothérapie interne du carcinome hépatocellulaire et du gliome

Abstract : Radiotherapy aims to preserve the irradiation of healthy tissues. For this purpose, lipid nanocapsules loaded with lipophilic complex of rhenium-188 (LNC188Re-SSS) were used to create a localized irradiation after intratumoral injection. Hence, we assessed the feasibility of internal radiation therapy after intra-hepatic LNC188Re-SSS for the treatment of hepatocellular carcinoma (HCC). Secondly, we examined the efficiency of repeated intracranial injections for the treatment of gliomas. The first part of this work describes the interest of internal radiotherapy with LNC188Re-SSS for the treatment of HCC with increased median survival up to 107% in a chemically-induced HCC rat model. Meanwhile, we demonstrated a major benefit in terms of survival, with 83% of animals which were long-term survivors. This therapeutic effect could be explained by the establishment of an adaptive immune response with local recruitment of immune effector cells (CD4+, CD8+...). However, assessment on a weakly immunogenic and radioresistant model (tumor model F98) showed lower benefits in terms of survival. To stimulate an anti-tumor immune response and to optimize therapeutic efficiency, we evaluate the combination of fractionated internal radiotherapy with vaccination of F98 irradiated cells. Although an increase in the recruitment of immune cells was highlighted, the combination of these two strategies did not result in better survival benefit. The prospects offered by this work are twofold: to assess the impact of the angiogenic process in the case of the HCC model and stimulate the immune system in combination with internal radiation therapy for the glioma model.
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Submitted on : Tuesday, January 31, 2012 - 11:43:59 AM
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  • HAL Id : tel-00664659, version 1

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Claire Vanpouille-Box. Les nanocapsules lipidiques chargées en Rhénium-188 : nouvel outil pour la radiothérapie interne du carcinome hépatocellulaire et du gliome. Sciences pharmaceutiques. Université d'Angers, 2011. Français. ⟨tel-00664659⟩

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