RADIOHEAD

The main purpose of the proposed work is to address the proof-of-principle evidence that internal radiotherapy through LNC188Re-SSS is a feasible treatment for glioblastomas that can be easily translate to clinical use. Attracting strong partnerships with an industrial company is althrough one of the main objective of this project (Partner 2). Therefore, this proposed work aims at providing evidences of the feasibility as well as to investigate the toxicity of an innovative technology: the LNC188Re-SSS. The expected results will lead to the establishment of the first phase I/II clinical trial of internal radiotherapy using nanoparticle. However, before using LNC188Re-SSS in clinic, requesting an authorization for a clinical trial to the Afssaps is mandatory (file AEC). This file includes a description of the clinical trial (DEC) as well as a detailed part on the experimental drug (DME). The DME part is composed of three subsets with the DME1 which provide informations on the chemistry quality of the drug; the DME2 will detail evidences concerning non clinical data and the DME3 will highlight clinical data. Therefore, the scientific program of this proposed work is divided into three phases. To meet with DME1 requirement, a fully automated formulation of high activity lipid nanocapsules loaded with rhenium-188 will be developed. For that purpose, radioprotected environments under a controlled atmosphere (laminar flow class A) will be used primarily in the PRIMEX facility (partners 1, 3, 4 and 7). The translation of this formulation process to the radiopharmacy of CHU of Angers will lead to the production of preclinic and clinic batches. Afterward, preclinic batches will provide missing data for the DME2 that are a robust dosimetry study (partner 5) as well as a toxicity evaluation (CERB Baugy). As soon as the toxicity study in animal model is performed, the submission of the AEC to the Afssaps will be realized to move toward the first phase I/II clinical trial of nanovectorized radiotherapy using lipid nanocapsules loaded with rhenium-188 for the treatment of patient diagnosed with a glioblastoma (partners 1, 6, 7 and 8).