Characterization of the distribution, retention, and efficacy of internal radiation of ¹⁸⁸Re-lipid nanocapsules in an immunocompromised human glioblastoma model

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 the ¹⁸⁸Re-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.