Improved protocol for the radiosynthesis of [¹⁸F]FTC-146: A potent and selective sigma-1 receptor radioligand

[18F]FTC-146 was introduced a decade ago as a very potent and selective sigma-1 receptor (σ1R) radioligand, which has shown promising application as an imaging agent for neuropathic pain with positron emission tomography (PET). In line with a multi-laboratory project on animal welfare, we chose this radioligand to investigate its potential for detecting neuropathic pain and tissue damage in tumor-bearing animals. However, the radiochemical yield (RCY) of around 4-7% was not satisfactory to us and efforts were made to improve it. Herein, we describe an improved approach for the radiosynthesis of [18F]FTC-146 resulting in a RCY, which is seven-fold higher than that recently reported by Shen et al. A tosylate precursor was synthesized and radio-fluorination experiments were performed via aliphatic nucleophilic substitution (SN2) reactions using either K[18F]F-Kryptofix®222 (K2.2.2)-carbonate system or tetra-n-butylammonium [18F]fluoride ([18F]TBAF). Several affecting reaction parameters such as solvent, 18F-fluorination agent with the corresponding amount of base, labeling time and temperature were investigated. Best labeling reaction conditions were found to be [18F]TBAF and acetonitrile as solvent at 100 °C. The new protocol was then translated to an automated procedure using a FX2 N synthesis module. Finally, the radiotracer could be reproducibly produced with a RCY of 41.7 ± 4.4% in high radiochemical purity (>98%) and molar activities up to 171 GBq/µmol.