Radiofluorination of oxazole-carboxamides for preclinical PET neuroimaging of GSK-3.

Autor: Varlow C; Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, M5T 1R8, Canada., Mossine AV; Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, United States., Bernard-Gauthier V; Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8, Canada., Scott PJH; Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, United States., Vasdev N; Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, M5T 1R8, Canada.
Jazyk: angličtina
Zdroj: Journal of fluorine chemistry [J Fluor Chem] 2021 May; Vol. 245. Date of Electronic Publication: 2021 Feb 21.
DOI: 10.1016/j.jfluchem.2021.109760
Abstrakt: 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.
Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Databáze: MEDLINE
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