One-step radiosynthesis of the MCTs imaging agent [18F]FACH by aliphatic 18F-labelling of a methylsulfonate precursor containing an unprotected carboxylic acid group

Abstract

AbstractMonocarboxylate transporters 1 and 4 (MCT1 and MCT4) are involved in tumour development and progression. Their level of expression is particularly upregulated in glycolytic cancer cells and accordingly MCTs are considered as promising drug targets for treatment of a variety of human cancers. The non-invasive imaging of these transporters in cancer patients via positron emission tomography (PET) is regarded to be valuable for the monitoring of therapeutic effects of MCT inhibitors. Recently, we developed the first 18F-radiolabelled MCT1/MCT4 inhibitor [18F]FACH and reported on a two-step one-pot radiosynthesis procedure. We herein describe now a unique one-step radiosynthesis of this radiotracer which is based on the approach of using a methylsulfonate (mesylate) precursor bearing an unprotected carboxylic acid function. With the new procedure unexpected high radiochemical yields of 43 ± 8% at the end of the radiosynthesis could be obtained in a strongly reduced total synthesis time. Moreover, the radiosynthesis was successfully transferred to a TRACERlab FX2 N synthesis module ready for future preclinical applications of [18F]FACH.