Nanocapsules for Selective Internal RadioTherapy of glioblastoma – RADIOHEAD

If the innovative radiopharmaceutical, nanocapsules labeled with Rhenium 188 (188Re-SSS-LNC), is well characterized at the laboratory scale, it is necessary to adapt the formulation process in order to have a process that complies with the regulations of the drug. The radioelement used, rhenium 188, comes from a generator compatible with a use in a radiopharmacy department and the radiation protection rules imply the development of an automated process. This step is an crucial aspect of this program as the activities involved can be important.
A second point required for transfer to the clinic is the biological evaluation of this new radiopharmaceutical. If the first results, which allowed the financing of this program, are remarkable especially in terms of efficacy, this evaluation must be supplemented by new investigations at the cellular level as on other animal models. Similarly, the dosimetric evaluation was carried out and a complementary program from the Cancéropôle Grand Ouest (IRAD), providing for an evaluation on canine model, has come to reinforce this Radiohead project. Finally, an acute and extensive toxicity study was included as an integral part of the Dossier de Medicament Experimental.

As the proposed work is to address the proof-of-principle evidence that internal radiotherapy through LNC188Re-SSS for glioblastomas can be translated to clinical use, attracting strong partnerships with two companies (Lemer-Pax, IRE) already involved, is althrough one of the main objective of this project.
Taken together, this proposal might at filling the gap of academic research, clinical institutions as well as compagnies to move toward a phase I/II clinical trial of a new treatment strategy for patient diagnosed with glioblastomas for whom no curative treatment is curently provided.

Radiohead has allowed the inclusion of the theme «vectored radiotherapy in the treatment of glioblastoma« as a unifying project within the IRON labex. Indeed, after presentation at the international scientific council of the iron labex, the experts supported this theme by its structuring character but also by the potential transfer to the clinic offered by the systems developed (188Re-SSS-LNC).

Already protected by two existing patents, the program has not given rise to new extensions. However, the automated formulation process as well as the regulatory toxicity study are important and necessary productions for the establishment of experimental drug status.

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).