Rapid preparation of [¹¹C]flumazenil: captive solvent synthesis combined with purification by analytical sized columns

Abstract

Abstract To produce the radioligand [ N ‐ methyl ‐ 11 C]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 µg). 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 ‐ 11 C]flumazenil from [ 11 C]iodomethane with radiochemical yields of 80% (decay corrected). This results in 8–10 GBq of [ N ‐ methyl ‐ 11 C]flumazenil at very high specific radioactivities of 520–600 GBq/µmol at the end‐of‐synthesis. The total preparation time from end‐of‐bombardment of cyclotron‐produced [ 11 C]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 © 2007 John Wiley & Sons, Ltd.