Synthesis of an 18F-labeled cyclin-dependent kinase-2 inhibitor

The radiosynthesis of N-(5-(((5-(tert-butyl) oxazol-2-yl) methyl) thio) thiazol-2-yl)-4-[F-18] fluoro-benzamide [F-18]2 as a potential radiotracer for molecular imaging of cyclin-dependent kinase-2 (CDK-2) expression in vivo by positron emission tomography is described. Two different synthesis routes were envisaged. The first approach followed direct radiofluorination of respective nitro-and trimethylammonium substituted benzamides as labeling precursors with no-carrier-added (n.c.a.) [F-18] fluoride. A second synthesis route was based on the acylation reaction of 2-aminothiazole derivative with labeling agent [F-18] SFB. Direct radiofluorination afforded F-18-labeled CDK-2 inhibitor in very low yields of 1%-3%, whereas acylation reaction with [F-18] SFB gave F-18-labeled CDK-2 inhibitor [F-18]2 in high yields of up to 85% based upon [F-18] SFB during the optimization experiments. Large scale preparation afforded radiotracer [F-18]2 in isolated radiochemical yields of 37%-44% (n = 3, decay-corrected) after HPLC purification within 75 min based upon [F-18] SFB. This corresponds to a decay-corrected radiochemical yield of 13%-16% based upon [F-18] fluoride. The radiochemical purity exceeded 95% and the specific activity was determined to be 20 GBq/mu mol.