Rapid preparation of (11C)flumazenil:: Captive solvent synthesis combined with purification by analytical sized columns

To produce the radioligand [N-methyl-C-11]flumazenil at very high specific radioactivity for our small animal imaging studies we have developed procedures for its rapid synthesis, purification and analysis. We have developed 'micro-reactor' apparatus which are assembled from analytical HPLC guard columns packed with stainless steel powder for performing the carbon-11 methylation reactions. These highly efficient reaction columns enable high radiochemical yields to be obtained with very small amounts of precursor (20-40 mu g). The very small amount of reactants used enables the use of small analytical-sized HPLC columns for the rapid purification of the radioligand. Combining these techniques has enabled us to consistently prepare [N-methyl-C-11]flumazenil from [C-11]iodomethane With radiochemical yields of 80% (decay corrected). This results in 8-10GBq of [N-methyl-C-11]flumazenil at very high specific radioactivities of 520-600 GBq/mu mol at the end-of-synthesis. The total preparation time from end-of-bombardment of cyclotron-produced [C-11]carbon dioxide to end-of-synthesis is 20 min. A quality control method based on very rapid HPLC analysis (completed within 2 min) on a micro-analytical HPLC column has also being developed to reduce the time from the end-of-synthesis to injection for imaging. Copyright (c) 2007 John Wiley & Sons, Ltd.