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

Abstract

The radiosynthesis of N‐(5‐(((5‐(tert‐butyl)oxazol‐2‐yl)methyl)thio)thiazol‐2‐yl)‐4‐[18F]fluoro‐benzamide [18F]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.) [18F]fluoride. A second synthesis route was based on the acylation reaction of 2‐aminothiazole derivative with labeling agent [18F]SFB. Direct radiofluorination afforded 18 F‐labeled CDK‐2 inhibitor in very low yields of 1%–3%, whereas acylation reaction with [18F]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 [18F]fluoride. The radiochemical purity exceeded 95% and the specific activity was determined to be 20 GBq/µmol. Copyright © 2011 John Wiley & Sons, Ltd.