Development and optimization of a novel automated loop method for production of [ 11 C]nicotine.

A novel, rapid, and automated loop method for the synthesis of [11 C]nicotine was developed and optimized. The method involves, a reaction of the precursor, (+) nornicotine or (-) nornicotine, with a gas-phase produced [11 C]CH3 I in an 800 µL loop at 75 °C for 5 min followed by a semi-preparatory Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) purification. The optimized synthesis and purification process was complete in < 30 min and produced [11 C]nicotine with > 99.9% Radiochemical Purity (RCP), no [11 C]CH3 I, no (+) nornicotine, 105 mCi/µmole specific activity, 7.0 - 7.2 pH, and 16.6% ethanol. The current method can be optimized, to reduce the ethanol content (<10%), and can be translated to a cGMP production of [11 C]nicotine for human clinical trials.