3. Development of New Stage Fluorination Methods for Synthesis of 18F-labeled Radioligands for PET Imaging.

Positron emission tomography (PET) is a powerful molecular imaging technology with important diagnostic applications in neurology, cardiology and oncology. An important feature of PET is that it can be used for direct study of the in vivo biochemical processes. The foremost PET radioisotope is 18F, which have a number of useful properties, such as high resolution and a half-life of 110 minutes. In addition organofluorines have very favorable pharmacokinetic properties including high metabolic stability in living organisms. These useful PET diagnostic properties suggest application of a broad variety of 18F labelled small (organic) molecules in PET imaging.


On the contrary, there are relatively few routinely applied fluorine-18 labelled radiotracers are available. An important reason for the poor availability of fluorinated radiotracers is the lack of a general synthetic solution for introducing 18F to organic substrates. The relatively short half-life of 18F involves that the fluorination have to be done in a late stage (preferentially in the last stage) in a multi-step synthesis. As a consequence, 18F have to be introduced with a high selectivity in an organic molecule, which already contains biologically relevant functionalities (for example, receptor binding groups). Solution of these synthetic problems is not trivial. However, in the last 5-7 years novel methodologies revolutionized the organic fluorine chemistry. Probably, the most important development has been a widespread application of metal catalysis and the use of novel electrophilic fluorination reagents in new synthetic procedures. These new procedures have helped to find new, efficient, late stage solutions for efficient synthesis of 18F PET tracers.


Our project is directed to collaboration between synthetic organic chemists at Stockholm University (SU) and PET radiochemists from AstraZeneca and Karolinska Institutet (KI) for development of new 18F PET tracers. The studies are directed to development of new fluorination methodologies, which are adapted to requirements of PET imaging. Our most important approach for introduction of 18F to PET tracers involves transition metal catalyzed electrophilic and nucleophilic fluorination methods. The main targets are prefunctionalized aromatics and alkenes but we will attempt to develop carbon-hydrogen bond functionalzation based methodologies as well. The main goal of the project is to find new fluorination methods that radiochemists can employ for synthesis of radioligands for PET studies.


Principle investigator: Kalman Szábó

Partner: AstraZeneca  (Magnus Schou)

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