1. Characterization of the distribution, retention, and efficacy of internal radiation of 188Re-lipid nanocapsules in an immunocompromised human glioblastoma model
- Author
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Nicolas Lepareur, Olivier Couturier, Philippe Menei, Anne Clavreul, Djamel Dabli, Francis Bouchet, François Hindré, Audrey Rousseau, Laurent Lemaire, Annabelle Cikankowitz, Clément Tétaud, Emmanuel Garcion, Animaux modèles pour la recherche en oncologie comparée (AMaROC), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), CIFAB-PRIMEX, Université d'Angers (UA), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de neurochirurgie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), CRLCC Eugène Marquis (CRLCC), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Médecine Nucléaire (Med Nuc - ANGERS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Plateforme de Radiobiologie et d’Imageries EXpérimentale [SFR ICAT - UA] (PRIMEX), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA)-Université d'Angers (UA), Service de neurochirurgie [CHU Angers], and Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Cancer Research ,Lipid nanocapsules ,medicine.medical_treatment ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Glioma ,medicine ,Convection-enhanced delivery ,Human glioblastoma ,Rhenium-188 ,business.industry ,Internal radiotherapy ,Internal radiation ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,medicine.disease ,Human situation ,3. Good health ,Radiation therapy ,Neurology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Toxicity ,Cancer research ,Neurology (clinical) ,business ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,030217 neurology & neurosurgery ,Glioblastoma - Abstract
International audience; Internal radiation strategies hold great promise for glioblastoma (GB) therapy. We previously developed a nanovectorized radiotherapy that consists of lipid nanocapsules loaded with a lipophilic complex of Rhenium-188 (LNC(188)Re-SSS). This approach resulted in an 83 % cure rate in the 9L rat glioma model, showing great promise. The efficacy of LNC(188)Re-SSS treatment was optimized through the induction of a T-cell immune response in this model, as it is highly immunogenic. However, this is not representative of the human situation where T-cell suppression is usually encountered in GB patients. Thus, in this study, we investigated the efficacy of LNC(188)Re-SSS in a human GB model implanted in T-cell deficient nude mice. We also analyzed the distribution and tissue retention of LNC(188)Re-SSS. We observed that intratumoral infusion of LNCs by CED led to their complete distribution throughout the tumor and peritumoral space without leakage into the contralateral hemisphere except when large volumes were used. Seventy percent of the (188)Re-SSS activity was present in the tumor region 24 h after LNC(188)Re-SSS injection and no toxicity was observed in the healthy brain. Double fractionated internal radiotherapy with LNC(188)Re-SSS triggered survival responses in the immunocompromised human GB model with a cure rate of 50 %, which was not observed with external radiotherapy. In conclusion, LNC(188)Re-SSS can induce long-term survival in an immunosuppressive environment, highlighting its potential for GB therapy.
- Published
- 2016
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