FLUOPET · Late Stage Fluorination for Positron Emission Tomography Applications
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2012-04-16 → 2015-04-15
- Финансиране от ЕС
- 264 113 €
- Участници
- 1
- Схема
- MC-IOF
Линиите свързват координатора с партньорите.
Накратко на български
Химията на флуора се изследва чрез създаване на нови методи за добавяне на този елемент към сложни молекули и лекарства. Това улеснява разработването на нови медикаменти и подобрява диагностиката на заболявания като рак и Алцхаймер чрез позитронна емисионна томография.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Late Stage Fluorination for Positron Emission Tomography Applications
Fluorine Chemistry is an extremely relevant research area that has enabled the discovery of new drugs and agrochemicals, the diagnostic imaging of diseases such as cancer and Alzheimer in humans via Positron Emission Tomography (PET) and the development of new materials. During this fellowship, important discoveries have been made, that will contribute to advance the field of fluorine chemistry, especially its applications in drug discovery and imaging. An operationally simple protocol for the selective 19F-deoxyfluorination of structurally complex molecules has been discovered. Several fluorinated derivatives of natural products and pharmaceuticals have been prepared to showcase the potential of the method. The work has been published in Journal of the American Chemical Society (J. Am. Chem. Soc. 2013, 135, 2470–2473) and the paper has been one of the 10 most accessed manuscripts during the period February-March. The reagent used in the discovered method is now commercialized by major fine-chemicals companies such as Aldrich and Strem. A new series of reagents for the perfluoroalkylation of organic molecules has been discovered. These new reagents allow the use of gaseous CF3I and CF3CF2I in a new formulation that renders them liquid and easy to handle, by making use of halogen-bonding interactions. The utility of the new reagents has been showcased in a large series of perfluoroalkylation reactions. The invention allows medicinal chemists and material chemists to prepare fluorinated compounds in a much easier way. The work has been published in Angewandte Chemie, International Edition (ACIE, 2015, 54, 3712–3716) and a patent application has been filed. The utility of the reagents has been highlighted in several Medicinal Chemistry Forums, such as Corante (http://pipeline.corante.com/archives/2015/03/03/put_away_the_lecture_bottle.php). A second area of impact for this fellowship has been in Positron Emission Tomography (PET). 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 such as fluorodeoxy-glucose (FDG) 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. During the third year of this fellowship, the radiosynthesis of two new compounds with potential application in imaging has been developed. The compounds are currently under investigation for the in vivo imaging of Fibroblast Activation Protein (FAP) and the receptor 5-HT3. Both receptors are highly important targets of current medicinal chemistry programs and are involved in several diseases such as cancer (FAP) and neurodegenerative dieseases (5-HT3).
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
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)""
Оригинален текст от CORDIS (на английски).
Участници
- EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH · ZuerichКоординаторШвейцария
Връзки
Данни: CORDIS, © Европейски съюз