Radiosynthesis and in vivo study of [18F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine: a promising new sigma-1 receptor ligand

• Published in: Journal of labelled compounds & radiopharmaceuticals 2005-07, Vol.48 (8), p.547-555
• Main Authors: Zhao, Jun, Chang, Raymond, Carambot, Patty, Waterhouse, Rikki N.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Contrast media. Radiopharmaceuticals; fluorine-18; Medical sciences; Miscellaneous; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; PET; Pharmacology. Drug treatments; radiotracer; sigma receptor
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.945

The novel sigma‐1 receptor PET radiotracer [18F]1‐(2‐fluoroethyl)‐4‐[(4‐cyanophenoxy)methyl]piperidine ([18F]WLS1.002, [18F]‐2) was synthesized (n=6) by heating the corresponding N‐ethylmesylate precursor in an anhydrous acetonitrile solution containing [18F]fluoride, Kryptofix K222 and potassium carbonate for 15 min. Purification was accomplished by reverse‐phase HPLC methods, providing [18F]‐2 in 59±8% radiochemical yield (EOB), with specific activity of 2.89±0.80 Ci/µmol (EOS) and radiochemical purity of 98.3±2.1%. Rat biodistribution studies revealed relatively high uptake in many organs known to contain sigma‐1 receptors, including the lungs, kidney, heart, spleen, and brain. Good clearance from normal tissues was observed over time. Blocking studies (60 min) demonstrated high (>80%) specific binding of [18F]‐2 in the brain, with reduction also noted in other organs known to express these sites. Copyright © 2005 John Wiley & Sons, Ltd.