Gas phase production of [<SUP>11</SUP>C]methyl iodide-d<INF>3</INF>. Synthesis and biological evaluation of <TOGGLE>S</TOGGLE>-[<TOGGLE>N</TOGGLE>-methyl-<SUP>11</SUP>C]citalopram and deuterated analogues

Three ¹¹C-labelled tracers for the serotonin reuptake site, S-[N-methyl-¹¹C]citalopram ([¹¹C]-4), S-[N-methyl-d<INF>3</INF>-¹¹C]citalopram ([¹¹C]-12), and S-[N-methyl-¹¹C]citalopram-α,α-d<INF>2</INF> ([¹¹C]-13) were synthesized and the distribution of radioactivity after injection of radioligand was examined ex vivo in rats. The deuterated analogue of (S)-desmethylcitalopram, (S)-1-(4-fluorophenyl)-1-(3-methylamino-[3-d<INF>2</INF>]-propyl)-1,3-di-hydro-isobenzofuran-5-carbonitrile (11), was synthesized in a multi-step synthesis from escitalopram (4) and used as precursor in the synthesis of [¹¹C]-13. In analogy with the reported gas phase synthesis of [¹¹C]methyl iodide the first gas phase synthesis of [¹¹C]Methyl iodide-d<INF>3</INF> is reported. The ¹H/²H kinetic isotope effect related to the synthesized compounds were investigated in ex vivo rat studies, where the brain regions of interest to cerebellum ratios of the tracers [¹¹C]-4, [¹¹C]-12 and [¹¹C]-13 were compared. The ex vivo data indicated no significant differences in binding in any of the investigated brain regions after injection of the three tracers. Copyright © 2004 John Wiley & Sons, Ltd.