Development and optimization of a novel automated loop method for production of [11C]nicotine. (October 2018)

• Record Type: Journal Article
• Authors: Ghosh, Arijit; Woolum, Karen; Knopp, Michael V.; Kumar, Krishan
• Is Part Of: Applied radiation and isotopes. Volume 140(2018:Oct.)
• Page Start: 76
• Page End: 82
• Publication Date: 2018-10
• Subjects: Radiosynthesis -- Radiotracers -- Gas-phase production of [11C]CH3I -- Automated loop method -- [11C]Nicotine; Radiology -- Periodicals; Radiation -- Industrial applications -- Periodicals; Nuclear chemistry -- Periodicals; Internet resource; Periodical; 660.298
• DOI: 10.1016/j.apradiso.2018.05.030
• Languages: English
• ISSNs: 0969-8043

Abstract

Abstract: 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. Highlights: A novel, rapid, and automated loop method for synthesis of [ 11 C]nicotine is reported. The reaction involves gas-phase produced 11CH3I and base form of (±) nornicotine or (-) nornicotine. The optimized process produced [ 11 C]nicotine with > 99.9% Radio Chemical Purity (RCP), no [ 11 C]CH3 I, no (±) nornicotine. An analytical HPLC method with a short run time was developed. The automated loop method for synthesis can be translated for GMP production of [ 11 C]nicotine for human clinical trials.