Radiofluorination of oxazole-carboxamides for preclinical PET neuroimaging of GSK-3.
J Fluor Chem
; 2452021 May.
Article
en En
| MEDLINE
| ID: mdl-33840834
ABSTRACT
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. [18F]OCM-49 was synthesized from [18F]fluoride using a copper-mediated reaction of an aryl boronic acid precursor, while [18F]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), [18F]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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
J Fluor Chem
Año:
2021
Tipo del documento:
Article
País de afiliación:
Canadá