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

[18 F]FTC-146 was introduced as a very potent and selective sigma-1 receptor radioligand, which has shown promising application as an imaging agent for neuropathic pain with positron emission tomography. 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 [18 F]FTC-146 resulting in a RCY, which is sevenfold higher than that previously reported. A tosylate precursor was synthesized and radio-fluorination experiments were performed via aliphatic nucleophilic substitution reactions using either K[18 F]F-Kryptofix®222 (K2.2.2 )-carbonate system or tetra-n-butylammonium [18 F]fluoride ([18 F]TBAF). Several parameters affecting the radiolabeling reaction such as solvent, 18 F-fluorination agent with the corresponding amount of base, labeling time, and temperature were investigated. Best labeling reaction conditions were found to be [18 F]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 reproducibly obtained with RCYs of 41.7 ± 4.4% in high radiochemical purity (>98%) and molar activities up to 171 GBq/µmol.

Mechanochemical Grignard Reactions with Gaseous CO2 and Sodium Methyl Carbonate.

A one-pot, three-step protocol for the preparation of Grignard reagents from organobromides in a ball mill and their subsequent reactions with gaseous carbon dioxide (CO2 ) or sodium methyl carbonate providing aryl and alkyl carboxylic acids in up to 82 % yield is reported. Noteworthy are the short reaction times and the significantly reduced solvent amounts [2.0 equiv. for liquid assisted grinding (LAG) conditions]. Unexpectedly, aryl bromides with methoxy substituents lead to symmetric ketones as major products.