Radiofluorination of oxazole-carboxamides for preclinical PET neuroimaging of GSK-3
| Autor: | Andrew V. Mossine, Cassis Varlow, Peter J. H. Scott, Vadim Bernard-Gauthier, Neil Vasdev |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.diagnostic_test
Aryl Organic Chemistry Neurodegeneration Standardized uptake value Pharmacology medicine.disease Biochemistry Article Inorganic Chemistry chemistry.chemical_compound chemistry Positron emission tomography GSK-3 medicine Environmental Chemistry Physical and Theoretical Chemistry Neuroinflammation Boronic acid Oxazole |
| Zdroj: | J Fluor Chem |
| ISSN: | 0022-1139 |
| Popis: | Glycogen synthase kinase 3 (GSK-3) is an enzyme that is dysregulated in oncology neurodegeneration, neuroinflammation and several mental health illnesses. As such, GSK-3 is a long-sought after target for positron emission tomography (PET) imaging and therapeutic intervention. Herein, we report on the development and radiofluorination of two oxazole-4-carboxamides, including one bearing a non-activated aromatic ring. Both compounds demonstrated excellent selectivity in a kinase screen and inhibit GSK-3 with high affinity. [(18)F]OCM-49 was synthesized from [(18)F]fluoride using a copper-mediated reaction of an aryl boronic acid precursor, while [(18)F]OCM-50 used a trimethylammonium triflate precursor, and both radiotracers were translated for preclinical PET imaging in rodents. Due to superior radiochemical yields and brain uptake (peak standardized uptake value of ~2.0), [(18)F]OCM-50 was further evaluated in non-human primate and also showed good brain uptake and rapid clearance. Further studies to consider clinical translation of both radiotracers are underway. |
| Databáze: | OpenAIRE |
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