SYNTHESIS OF [F-18] 3-FLUOROPROPYL)-4-(4-CYANOPHENOXYMETHYL)PIPERIDINE - A POTENTIAL SIGMA-1 RECEPTOR RADIOLIGAND FOR PET

3-Fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine has been prepared a s a potential sigma-1 receptor ligand for PET. The unlabeled ligand wa s 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 receptor s 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. R adiofluorination was accomplished using nucleophilic fluorination meth ods using an alkylmesylate precursor and the specific activity of the product was >74,000 MBq/mu mole. The average radiochemical chemical yi eld after purification was 62.3 +/- 5.2% (56-70% EOB; n = 5) and the r adiochemical purity of the product was >99%. The average time of synth esis and purification was 80 minutes.