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

✍ Scribed by Marcel C. Cleij; John C. Clark; Jean-Claude Baron; Franklin I. Aigbirhio


Book ID
102367952
Publisher
John Wiley and Sons
Year
2007
Tongue
French
Weight
119 KB
Volume
50
Category
Article
ISSN
0022-2135

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✦ Synopsis


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 mg). 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/mmol at the end-of-synthesis. The total preparation time from endof-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.