Synthesis of 18F labeled clotrimazole derivatives as a potential PET imaging agent

Clotrimazole [1-<(2-chlorophenyl)-diphenylmethyl>-1H-imidazole, CLT] has been reported to inhibit the proliferation of vascular endothelial and act as an in vitro anti-VEGF drug. It is also shown to inhibit angiogenesis in an animal model. The radioisotope labeled clotrimazole derivative can be utilized to monitor the physiologic processes of cancer. In this study, we synthesized [18F]fluoride labeled clotrimazole derivatives as a new tumor imaging agent for PET. The references were prepared by a refluxing with clotrimazole and an excess of fluoroalkyltosylate in acetonitrile for 36 h and clotrimazole reacted with ditosylalkane to give precursors. [18]Fluoride labeled reaction was performed with precursor in Kryptofix[2.2.2]/K2CO3 for 10 min at 80 .deg. C. The radiolabeling mixture was passed through a silica Sep-Pak cartridge to remove 18F-. The [18]F-clotrimazole derivatives were synthesized with a 20 ∼ 25% yield. In the radiofluoriantion step, we used acetonitrile and DMSO as a solvent and observed a higher at the acetonitrile (25%) reaction compared with the DMSO reaction (5%)