Synthesis and evaluation of [O-methyl-¹¹C]4-[3-[4-(2- methoxyphenyl)- piperazin-1-yl]propoxy]-4-aza-tricyclo[5.2.1.02,6]dec-8-ene-3,5- dione as a 5-HT_1A receptor agonist PET ligand

4-[3-[4-(2-Methoxyphenyl)piperazin-1-yl]propoxy]-4-aza-tricyclo[5.2.1.02,6] dec-8-ene-3,5-dione (4), a potent and selective 5-HT_1A agonist, was labeled by ¹¹C-methylation of the corresponding desmethyl analogue 3 with ¹¹C-methyl triflate. The precursor molecule 3 was synthesized from commercially available endo-N-hydroxy-5-norbornene-2,3-dicarboximide in two steps with an overall yield of 40%. Radiosynthesis of ¹¹C-4 was achieved in 35 min in 20 ± 5% yield (n = 6) at the end of synthesis with a specific activity of 2600 ± 250 Ci/mmol. In vivo positron emission tomography (PET) studies in baboon revealed rapid uptake of the tracer into the brain. However, lack of specific binding indicates that ¹¹C-4 is not useful as a 5-HT_1A agonist PET ligand for clinical studies.