PRISMAP - Anna Krzyczmonik, Gopi Elumalai
PRISMAP Call 2024–1
Novel prosthetic groups for the 211At-astatination of biomolecules via disulphide rebridging
The PRISMAP Consortium brings together key European, national, and regional research infrastructures selected for their expertise in the production, processing, and distribution of non-conventional radionuclides.
Through a project granted within the PRISMAP programme, two researchers from the NOMATEN Centre of Excellence, Dr Anna Krzyczmonik and Dr Gopi Elumalai, obtained access to the research infrastructure and laboratories of GIP ARRONAX (Accelerator for Research in Radiochemistry and Oncology in Nantes-Atlantique) in Saint-Herblain, France. The ARRONAX facility operates a high-energy particle cyclotron dedicated to research in nuclear medicine and radiochemistry.
During the research visit, the short-lived alpha-particle-emitting radionuclide astatine-211 (211At) was produced and separated at the ARRONAX facility. The researchers from NOMATEN subsequently performed radiolabelling studies using 211At and novel prosthetic groups synthesized within their research programme. Access to this unique research infrastructure significantly expanded the experimental capabilities of the NOMATEN researchers and enabled studies with a radionuclide that remains difficult to access through conventional commercial sources.
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 rebridging. 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.
Link to the webpage:
