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

✍ Scribed by T. Lee Collier; Joanne C. O'Brien; Rikki N. Waterhouse

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 467 KB
• Volume: 38
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/(sici)1099-1344(199609)38:9<785::aid-jlcr901>3.0.co;2-b

✦ Synopsis

~F]-1-(3-Fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine has been prepared as a potential sigma-I receptor ligand for PET. The unlabeled ligand was found to be selective in vitro for the sigma-I receptor [Ki(crl) = 4.3 nM] when tested in a variety of neuroreceptor binding assays. Furthermore, the ligand is selective for sigma-I over sigma-2 receptors in vitro, having only moderate affinity for the sigma-2 receptor [Ki(a2) = 144 nM)]. The lipophilicity of the ligand (log P7.5 = 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/pmole. The average radiochemical chemical yield after purification was 62.3 k 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.