Preparation and Preliminary Imaging Study of Molecular Probe ［18F］FEtO-CHC Targeting Monocarboxylic Acid Transporter

Abstract

Using α-cyano-4-hydroxy-cinnamic acid, a small molecule inhibitor of monocarboxylic acid transporters(MCTs), as the lead compound, a novel 18F-labeled α-cyano-4-hydroxy-cinnamic acid probe was designed and synthesized. The preliminary evaluation of stability and tumor PET/CT imaging were performed in this study. Taking α-cyano-4-(2-p-toluenesulfonyl-ethoxy)-methyl cinnamate as the precursor compound, the intermediate compound α-cyano-4-(2-［18F］-fluoroethoxy)-methyl cinnamate(［18F］4) was obtained by nucleophilic reaction with 18F-, which was separated and purified by high performance liquid chromatography(HPLC). α-cyano-4-(2-［18F］-fluoroethoxy)-cinnamic acid(［18F］FEtO-CHC, ［18F］5) can be obtained from the hydrolysis of ［18F］4 with 2 mol/L NaOH solution and the neutralization with 1 mol/L HCl solution. The results of cell proliferation inhibition assay show that compound ［19F］5 has better inhibitory activity than that of CHC. ［18F］FEtO-CHC shows good stability and biosafety from the in vitro and in vivo studies, and micro-PET/CT imaging in DU145 prostate cancer tumor-bearing mice shows that ［18F］5 has obvious radioactive accumulation at the tumor site. ［18F］FEtO-CHC has the advantages of simple synthesis process, good stability, high biological safety, and ability for tumor PET imaging. It is a potential PET agent for specific MCTs imaging.

Keywords

• monocarboxylic acid transporter
• metabolism of symbiosis
• α-cyano-4-hydroxy-cinnamic acid
• pet imaging probe
• radiochemical synthesis