Lu-177 labelled Rituximab - new approach to have suitable radiopharmaceutical

摘要

The purpose of this investigation was to introduce a technology for the production of ready-to-use cold kit formulations for the labelling of conjugated DOTA-Rituximab with Lu-177, and to standardize the methods for synthesis and conjugation. In a parallel study, the biological properties and pharmacokinetic behaviors of radiolabelled DOTA-Rituximab were investigated to compare and determine their toxicities and therapeutic efficacies using model systems comprising both isolated cell cultures and laboratory animals.udDTPA- or DOTA- chelated antibodies have been proved to be effective in radioimmunotherapy of cancer after radiolabelling with beta-emmiting radionuclides. The standardization of methods for conjugation of suitable chelators to monoclonal antibodies and the further pharmaceutical development of these conjugates were planned within the framework of an IAEA coordinated research project aimed at developing radiopharmaceuticals labelled with Lu-177.udTherefore, our study was focused on the development of a freeze-dried kit formulation based on DOTA-antiCD20 Rituximab for Lu-177 labeling, as a potential radiopharmaceutical for radionuclide therapy.udFor this reason, the first part of our work was devoted to establish an efficient freeze-drying procedure for developing a final kit formulation for simple antibody labeling. The procedure for freeze-drying should provide a stable ready-to-use kit formulation, having the same labeling efficiency as established for the freshly prepared laboratory preparation. The freeze-dried formulation should preserve the same immunoreactivity of the antibody before and after conjugation as already observed for the liquid formulation. For this reason, we focused our study on the evaluation of the most important steps required to set up a suitable freeze-drying protocol and, in particular, to estimate the optimal time for lyophilization of the monoclonal antibody during each phase of the process, e.g. (a)pre-freezing, (b) primary drying, and (c) secondary drying. ud