Synthesis of [F-18]-1-(3-fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine: A potential sigma-1 receptor radioligand for PET

[F-18]-1-(3-Fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine has been prepared as a potential sigma-1 receptor ligand for PET. The unlabeled ligand was found to be selective in vitro for the sigma-1 receptor [Ki(sigma(1)) = 4.3 nM] when tested in a variety of neuroreceptor binding assays. Furthermore, the ligand is selective for sigma-1 over sigma-2 receptors in vitro, having only moderate affinity for the sigma-2 receptor [Ki(sigma 2) = 144 nM)]. The lipophilicity of the ligand (log P-7.5 = 2.8) is appropriate for good brain uptake and low non-specific binding. Radiofluorination was accomplished using nucleophilic fluorination methods using an alkylmesylate precursor and the specific activity of the product was >74,000 MBq/mu mole. The average radiochemical chemical yield after purification was 62.3 +/- 5.2% (56-70% EOB; n = 5) and the radiochemical purity of the product was >99%. The average time of synthesis and purification was 80 minutes.