Facile synthesis of carbon-11-labeled arylpiperazinylthioalkyl derivatives as new PET radioligands for imaging of 5-HT1AR

Carbon-11-labeled arylpiperazinylthioalkyl derivatives, 2-((4-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)butyl)thio)benzo[d]oxazole ([11C]5a), 2-((4-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)butyl)thio)-5,7-dimethylbenzo[d]oxazole ([11C]5c), 2-((4-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)butyl)thio)benzo[d]thiazole ([11C]5e), 2-((6-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)hexyl)thio)benzo[d]oxazole ([11C]5g), 2-((6-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)hexyl)thio)-5,7-dimethylbenzo[d]oxazole ([11C]5i), and 2-((6-(4-(2-[11C]methoxyphenyl)piperazin-1-yl)hexyl)thio)benzo[d]thiazole ([11C]5k), were prepared from their corresponding phenol precursors with [11C]CH3OTf through O-[11C]methylation and isolated by a simplified solid-phase extraction (SPE) method using a Sep-Pak Plus C18 cartridge in 50–60% (n=5) radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5±92.5 GBq/μmol (n=5).

► New arylpiperazinylthioalkyl derivatives were synthesized.
► New carbon-11-labeled arylpiperazinylthioalkyl derivatives were synthesized.
► Simplified solid-phase extraction (SPE) method was employed in radiosynthesis.