PRISMAP - Anna Krzyczmonik, Gopi Elumalai

Title: Novel prosthetic groups for the 211At-astatination of biomolecules via disulphide rebridging.

Abstract: Disulphide rebridging is a site-specific bioconjugation of prosthetic groups to biomolecules. Most therapeutically relevant biomolecules contain at least one disulphide bridge available for the construction of disulphide rebridge. This strategy proved to be an effective for the functionalization of peptides, monoclonal antibodies, and their fragments. However, the potential of rebridging strategy has received relatively little attention in the context of radiolabelling. During the course of the project, we would like to explore the potential of this technique in application to radiotherapy. Currently, our group is researching the application of this technique to therapy with iodine-131, during this project we would like to test the application to targeted alpha therapy. Astatine-211 is an α-emitting radionuclide and is currently of major interest for the development of therapeutic radiopharmaceuticals since α-therapy is gaining tremendous attention nowadays. Astatine-211 has a convenient half-life of 7.21 h, which is long enough to perform an effective treatment. The specific goal of this project is to develop new prosthetic groups for astatination of biomolecules via disulphide rebridging. We have prepared prosthetic groups with suitable leaving groups allowing radiohalogen labelling to be carried out. In addition, we would like to test heterocyclic-based prosthetic groups, the structure of which should help to stabilise the carbon-astatine bond to reduce the risk of deastatination in vivo. Initial labelling studies, conjugation with octreotide and in vitro testing of the compounds produced will first be carried out with iodine-131 to develop the best reaction parameters and select the most promising prosthetic groups for further testing. Once positive results are obtained, we will carry out labelling with astatine-211 and the resulting astatinated prosthetic groups conjugated with octreotide via disulphide rebridging will be tested in primary in vitro studies.



This project has received funding from the European Union Horizon 2020 research and innovation
programme under grant agreement No 857470 and from European Regional Development Fund
via Foundation for Polish Science International Research Agenda PLUS programme grant
No MAB PLUS/2018/8.
Poland
The project is co-financed from the state budget within the framework of the undertaking of the Minister of Science and Higher Education "Support for the activities of Centers of Excellence established under Horizon 2020".

Grant: 5 143 237,70 EUR
Total value: 29 971 365,00 EUR
Date of signing the funding agreement: December 2023

The purpose of the undertaking is to support entities of the higher education and science system that have received funding from the European Union budget in the competition H2020-WIDESPREAD-2018-2020/WIDESPREAD-01-2018-2019: Teaming Phase 2. in the preparation, implementation and updating of activities, maintenance of material resources necessary for carrying out activities, acquisition and modernization of scientific and research apparatus, maintenance and development of personnel potential necessary for the implementation of activities, and dissemination of the results of scientific activities.