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

摘要

The radiosynthesis of N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-4-[~(18)F]fluoro-benzamide [~(18)F]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.) [~(18)F]fluo-ride. A second synthesis route was based on the acylation reaction of 2-aminothiazole derivative with labeling agent [~(18)F] SFB. Direct radiofluorination afforded ~(18)F-labeled CDK-2 inhibitor in very low yields of 1%-3%, whereas acylation reaction with [~(18)F]SFB gave ~(18)F-labeled CDK-2 inhibitor [~(18)F]2 in high yields of up to 85% based upon [~(18)F]SFB during the optimization experiments. Large scale preparation afforded radiotracer [~(18)F]2 in isolated radiochemical yields of 37%-44% (n = 3, decay-corrected) after HPLC purification within 75 min based upon [~(18)F]SFB. This corresponds to a decay-corrected radiochemical yield of 13%-16% based upon [~(18)F]fluoride. The radiochemical purity exceeded 95% and the specific activity was determined to be 20 GBq/mumol.