Efficient in-loop synthesis of high specific radioactivity [ 11C]carfentanil

Abstract

The synthesis of the precursor for [11C]carfentanil and the precursor labelling with 11C have both been improved. The problem 'bottleneck' step in the carfentanil precursor synthesis, due to low chemical yield (14%) of intermediates nitrile into amide conversion, has been solved. Application of a H2O2/K2CO3/DMSO reaction method significantly increased the yield of this chemical transformation (up to 84%). A simple and straight-forward synthesis of [ 11C]carfentanil was achieved by combining in-loop methylation of the ammonia salt of the precursor by [11C]CH3I, using tetrabutylammonium hydroxide as a base, with a previously developed product purification procedure using a C2 extraction disc. A decay corrected yield with respect to [11C]CH3I of [11C]carfentanil was 64 ± 12% (n = 6) with the synthesis time of 21 min. The radiochemical purity was >98%. Comparatively high specific radioactivity of [ 11C]carfentanil [11.2 ± 4.8Ci/ μmol (EOS, n= 5)] was partially attributed to the use of [11C]methane target gas for production of carbon-11 methyl iodide. Copyright © 2003 John Wiley & Sons, Ltd.