Synthesis of 5-HT3 receptor antagonists, [11C]Y-25130 and [11C]YM060.

Two high-affinity 5-HT3 receptor ligands, Y-25130 and YM 060, have been labeled with 11C for use in PET studies to measure 5-HT3 receptors. The [11C]Y-25130 was prepared by N-methylation of nor-Y-25130-BH3 complex with [11C]CH3I in the presence of K2CO3 followed by HCl hydrolysis. Likewise, N-methylation of nor-YM060 gave [11C]YM060. After HPLC separation, the decay-corrected radiochemical yield of the two 11C-labeled ligands was 34-40% based on [11C]CH3I, the specific activity was 10-12 GBq/mumol at 35-40 min from EOB, and the radiochemical and chemical purities were > 99%. In mice, the brain uptake of the two compounds was the lowest among the tissues investigated, but the level of the brain radioactivity increased with time.