Synthesis and in vitro characterization of trans- and cis-[18F]-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoropiperidine-1-carboxylates as new potential PET radiotracer candidates for the NR2B subtype N-methyl-d-aspartate receptor

Diastereoisomeric compounds [18F]cis- and [18F]trans-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoro-piperidine-1-carboxylates were successfully synthesized as new subtype-selective PET radiotracers for imaging the NR2B subunit containing NMDA receptors. Rat brain section autoradiographies demonstrated a high specific binding in NR2B/NMDA receptor rich regions for both radioligands. The measured logD7.4 values as well as Bmax/Kd ratios indicated that both radiotracers possess the adequate properties required for PET radiotracers.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Two diastereoisomeric NR2B NMDA antagonists were radiolabelled with fluorine-18. ► The radiolabelling of 3-[18F]fluoro-1,4-substituted-piperidine pattern was achieved. ► In vitro study showed high specific and selective binding for NR2B NMDAR receptors. ► Bmax/Kd ratios and logD7.4 demonstrated appropriate properties for in vivo imaging.