Cutting-edge radiosynthesis solutions for preclinical and clinical PET imaging in Norway

Medical imaging with positron emission tomography has led to an ever growing knowledge and understanding of disease. Nevertheless, the technology to study disease without disturbing normal function using PET imaging relies on new radioactive, chemical probes tailored to each disease. The value of PET for clinical investigations has been recognised in Norway resulting in major investments to make PET available for patients. Within this project we have built a sustainable foundation for the development of suitable PET radiotracers by training of PET scientists in the development of novel radiopharmaceuticals: - A metal free method for radiosynthesis published in 2017 has been applied preclinical use in dementia in 2019 - New radiopharmaceuticals based on fluorine-18 labelled ligands to study cellular damage and neurodegeneration were tested in patients - An 11C-labelled NMDA ligand was developed for PET in brain and a new labelling method for 18F has been developed in 2020.

We built a training program in PET radiochemistry at UiO. In the program 2 BSc students, 4 MSc students, 9 PhD students and 2 postdocs were trained in theory and practice of radiopharmaceutical sciences and PET imaging. At present, 2 PhD students and 1 postdoc are completing their research on cutting-edge radiosynthesis solutions for preclinical and clinical PET imaging in Norway in the spirit of the original grant. In the project, we published 12 scientific articles in reputed international journals. 2 translational clinical studies were made possible by the project, 3 level 2 publications and 1 cover picture were subsequently highlighted by the research community. The PET program is active until 2022 due to financial support from other sources so the project will lead to 1 further new radiotracer for Parkinson's disease and 2 metal-free labelling methods. We successfully implemented our aims in this project, sadly, no further funding was obtained from NFR to continue in the future.

Novel PET radiotracers are essential to study neurochemical processes in vivo in animals and humans. This project is concerned with the development of 11C and 18F labelling methods for application in radiotracer synthesis. The novel methodology will be em ployed to synthesise radiolabelled analogues of known drugs followed by preclinical validation in rats. The labelled molecules will be useful for the study of molecular mechanisms of neurological and psychiatric diseases in the context of ongoing research in Oslo. The project comprises three work packages (WP): WP1 will emphasise proliferation and training of experts in PET chemistry and PET imaging. The fast growth of national PET infrastructure in Norway generates a need of staff scientists and research ers, which is currently unmet. The Oslo PET environment provides an excellent combination of experts, state-of-the-art PET and radiochemistry facilities which are fully accessible for training and teaching. WP2 will emphasise radiolabelling with 11C and 1 8F, two excellent PET radionuclides. We will target CF3 groups, which are difficult to label with 18F. Furthermore a versatile platform for 11C labelling will be developed based on 11CO2, one of two primary products in the production of 11C. 11C labellin g is the most elegant and straightforward way of synthesizing a PET radiotracer simply by substitution of a stable carbon atom in the molecule. The main culprit for the application of 11C is the short half-life of 20 minutes in conjunction with the elabor ate conversion of 11CO2 into useful labelling reagents. We will overcome the limitations by developing novel labelling methods for direct conversion of 11CO2 into radiotracers. WP3 will emphasise a combination of the novel methodology developed in WP2 usi ng a paradigm of repositioning known drug molecules as PET radiotracers. Due to the safe ADMET profiles of approved drug molecules human application can be achieved straightforwardly.