Synthesis of [ 18 F]fluoroalkyl esters of carfentanil

With the aim to develop and evaluate new ligands for depicting the µ‐opioid receptor with positron emission tomography, the 18 F‐fluoroalkyl esters of carfentanil, 3‐carboxy‐(2‐[ 18 F]fluoroethyl)fentanyl, (2‐[ 18 F]fluoroethyl‐carfentanil) and 3‐carboxy‐(3‐[ 18 F]fluoropropyl)fentanyl (3‐[ 18 F]fluoropropyl‐carfentanil) were prepared by a two‐step radiosynthesis. Reacting carfentanil carboxylate sodium salt, added 0.96 eqv. of tetrabutyl ammonium hydroxide (TBAH), with no‐carrier‐added (n.c.a.) 2‐[ 18 F]fluoroethyltosylate for 20 min at 150°C in dimethyl formamide (DMF) provided 2‐[ 18 F]fluoroethyl carfentanil in an isolated radiochemical yield (RCY) of 36 ± 8%, a specific activity ( S A ) of 35 ± 5 TBq/mmol ( n =4) within a synthesis time of ∼100 min. Similarly, 3‐[ 18 F]fluoropropyl carfentanil could be obtained by reacting the carfentanil TBA/Na salt with 3‐[ 18 F]fluoropropyl iodide at 160°C in DMF (isolated RCY=6 ± 2%; ∼100 min, S A =27 ± 5 TBq/mmol, n =4). The developed methods allow the production of the two 18 F‐labeled carfentanil derivatives in amounts and specific activities necessary and relevant for a detailed preclinical evaluation of these new potential µ‐opioid receptor ligands in vitro and in animal models. Copyright © 2005 John Wiley & Sons, Ltd.