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-[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 ¹⁸F-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/mmol.