Radiosynthesis of a new alpha-2C-adrenoceptor tracer [11C]ORM-13070 and its preclinical evaluation in rats

Methods: [C]ORM-13070 (1-[(S)-1-(2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]-4-(3-C-methoxymethylpyridin-2-yl)-piperazine) was synthesized by C-methylation of O-desmethyl-ORM-13070 with [C]methyl triflate prepared from cyclotron-produced [C]methane via [C]methyl iodide. [C]Methyl triflate was bubbled through a solution of desmethyl-precursor in acetonitrile in the presence of TBAOH. The reaction mixture was heated for 3 min at 80 °C and purified with semi-preparative HPLC. The biodistribution of radioactivity after [C]ORM13070 injection was studied ex vivo in rat brain using autoradiography. The specific binding of [C]ORM-13070 was estimated from in vivo blocking experiments with atipamezole, a specific antagonist for α2-receptors.