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Late Stage Fluorination for Positron Emission Tomography Applications (FLUOPET)
Start date: Apr 16, 2012, End date: Apr 15, 2015 PROJECT  FINISHED 

"Positron Emission Tomography (PET) is a powerful non-invasive, real-time imaging technology that can be used to identify and characterize human disease, but is currently limited by deficiencies in chemistry. While simple molecules can be efficiently prepared, more complex, biomedically interesting molecules often cannot. The short half-life of [18F] (110 min) dictates severe restrictions on the chemical synthesis of PET tracers. Fluoride introduction must occur at a late stage of the synthesis, ideally as the last step, to avoid unproductive decay of the [18F] nucleus before injection into the body. Due to the limited functional group compatibility with conventional fluorination reactions employed today and the short half-life, the synthesis of PET tracers is limited to a small number of simple molecules. The high specific-activity isotopes – thus low mass – dictate a need for unusually high chemical reaction rates and efficiencies, which are met by only a handful of methods.The Ritter group at Harvard has developed a unique technology based on the concept of late-stage fluorination as a tool to streamline the synthesis of complex fluorinated molecules using [19F]. Late-stage fluorination has the potential of significantly increasing the number of [18F]-PET agents and their radiochemical yield. During this Fellowship we wish to develop and validate a general and robust late-stage fluorination chemistry with [18F] for the synthesis of PET tracers, using the “know how” of the Ritter group in the field of modern C-F bond formation.The new technology developed will be initially applied to the preparation of [18F]-fluorodeoxyestrone as a first “proof of concept”. In a more advanced stage, the project will deal with the translation of the new technology from Harvard to the ETH Centre for Radiopharmaceutical Science (Ametamey group), where will be used for the preparation of new [18F]-PET tracers for imaging PET the Metabotropic Glutamate Receptor Subtype 5 (mGluR5)"
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