Radiosynthesis and preliminary evaluation of [11C] and [18F] labelled lacosamide scaffolds for brain PET imaging.

Abstract

This study summarizes the automated, transition-metal-free radiosynthesis approach for producing [11C]LCM and its bioisosteric analogue [18F]FLCM, along with preliminary pharmacological and preclinical evaluations of these radiotracers can act as potent brain imaging radiotracer candidates. Radiosynthesis was carried out using an automated synthesis module targeting the terminal 3-oxy site of lacosamide. Physicochemical properties, including hydrophilic behavior and plasma-protein binding profile, were evaluated. Translational validation was performed via in vivo PET/CT imaging and ex vivo biodistribution in healthy Wistar rats. The synthesis module yielded a radiotracer with high radiochemical yield and radiochemical purity. Specific activity was determined to be ~21 .7GBq/μmol for [11C]LCM and ~6.76 GBq/μmole for [18F]FLCM. Both radiotracers show favorable hydrophilic and low PPB profiles. In vivo PET scan and ex vivo study confirmed the brain uptake, renal and hepatic clearance, and minimal off-target uptake. The favorable pharmaceutical profiles establish a promising baseline, further rigorous in vitro receptor-affinity assays and dynamic brain imaging in an animal model are required to validate the translational diagnostic utility of these radiotracers.