title: Characterization of the distribution, retention, and efficacy of internal radiation of188Re-lipid nanocapsules in an immunocompromised human glioblastoma model.
abstract: 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 (LNC188Re-SSS). This approach resulted in an 83 % cure rate in the 9L rat glioma model, showing great promise. The efficacy of LNC188Re-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 LNC188Re-SSS in a human GB model implanted in T-cell deficient nude mice. We also analyzed the distribution and tissue retention of LNC188Re-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 the188Re-SSS activity was present in the tumor region 24 h after LNC188Re-SSS injection and no toxicity was observed in the healthy brain. Double fractionated internal radiotherapy with LNC188Re-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, LNC188Re-SSS can induce long-term survival in an immunosuppressive environment, highlighting its potential for GB therapy.
authors: INSERM U1066 MINT (Micro et Nanomédecines Biomimétiques), Université d'Angers, Angers, France.|AMaROC, ONIRIS, Ecole Nationale Véterinaire de Nantes, Nantes, France.|PRIMEX (Plateforme de Radiobiologie et d'Imagerie Expérimentale), Université d'Angers, Angers, France.
authors: Annabelle
authors: A
authors: Cikankowitz
authors: INSERM U1066 MINT (Micro et Nanomédecines Biomimétiques), Université d'Angers, Angers, France. anne.clavreul@univ-angers.fr.|Service de Neurochirurgie, CHU d'Angers, Angers, France. anne.clavreul@univ-angers.fr.
authors: Anne
authors: A
authors: Clavreul
authors: INSERM U1066 MINT (Micro et Nanomédecines Biomimétiques), Université d'Angers, Angers, France.|PRIMEX (Plateforme de Radiobiologie et d'Imagerie Expérimentale), Université d'Angers, Angers, France.
authors: Clément
authors: C
authors: Tétaud
authors: INSERM U1066 MINT (Micro et Nanomédecines Biomimétiques), Université d'Angers, Angers, France.
authors: Laurent
authors: L
authors: Lemaire
authors: Laboratoire de Pathologie Cellulaire et Tissulaire, CHU d'Angers, Angers, France.
authors: Audrey
authors: A
authors: Rousseau
authors: Centre Régional de Lutte Contre le Cancer (CRLCC) Eugène Marquis, Rennes, France.
authors: Nicolas
authors: N
authors: Lepareur
authors: Médecine Nucléaire et Biophysique, CHU d'Angers, Angers, France.
authors: Djamel
authors: D
authors: Dabli
authors: Médecine Nucléaire et Biophysique, CHU d'Angers, Angers, France.
authors: Francis
authors: F
authors: Bouchet
authors: INSERM U1066 MINT (Micro et Nanomédecines Biomimétiques), Université d'Angers, Angers, France.
authors: Emmanuel
authors: E
authors: Garcion
authors: INSERM U1066 MINT (Micro et Nanomédecines Biomimétiques), Université d'Angers, Angers, France.|Service de Neurochirurgie, CHU d'Angers, Angers, France.
authors: Philippe
authors: P
authors: Menei
authors: INSERM U1066 MINT (Micro et Nanomédecines Biomimétiques), Université d'Angers, Angers, France.|Médecine Nucléaire et Biophysique, CHU d'Angers, Angers, France.
authors: Olivier
authors: O
authors: Couturier
authors: INSERM U1066 MINT (Micro et Nanomédecines Biomimétiques), Université d'Angers, Angers, France.|PRIMEX (Plateforme de Radiobiologie et d'Imagerie Expérimentale), Université d'Angers, Angers, France.
authors: François
authors: F
authors: Hindré
mesh_terms: D000818:Animals; D001345:Autoradiography; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage / Q000627:therapeutic use*; D011868:Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D012211:Rhenium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000473:pathology; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D053769:Nanocapsules; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C000615081:Rhenium-188; D012211:Rhenium
keywords: Convection-enhanced delivery; Human glioblastoma; Internal radiotherapy; Lipid nanocapsules; Rhenium-188