Radiosynthesis of 3‐(2′‐[¹⁸F]fluoro)‐flumazenil ([¹⁸F]FFMZ)

Abstract

Abstract Recently, two fluorine‐18 labelled derivatives of flumazenil were described: 5‐(2′‐[ 18 F]fluoroethyl)‐5‐desmethylflumazenil (ethyl 8‐fluoro‐5‐[ 18 F]fluoroethyl‐6‐oxo‐5,6‐dihydro‐4 H ‐benzo‐[ f ]imidazo[1,5‐ a ] [1,4]diazepine‐3‐carboxylate; [ 18 F]FEFMZ) and 3‐(2′‐[ 18 F]fluoro)‐flumazenil (2′‐[ 18 F]fluoroethyl 8‐fluoro‐5‐methyl‐6‐oxo‐5,6‐dihydro‐4 H ‐benzo‐[ f ]imidazo[1,5‐ a ]‐[1,4]diazepine‐3‐carbo‐ xylate; [ 18 F]FFMZ). Since the biodistribution data of the latter were superior to those of the former we developed a synthetic approach for [ 18 F]FFMZ starting from a commercially available precursor, thereby obviating the need to prepare a precursor by ourselves. The following two‐step procedure was developed: First, [ 18 F]fluoride was reacted with 2‐bromoethyl triflate using the kryptofix/acetonitrile method to yield 2‐bromo‐[ 18 F]fluoroethane ([ 18 F]BFE). In the second step, distilled [ 18 F]BFE was reacted with the tetrabutylammonium salt of 3‐desethylflumazenil (8‐fluoro‐5‐methyl‐6‐oxo‐5,6‐dihydro‐4 H ‐benzo‐[ f ]imidazo[1,5‐ a ] [1,4]diazepine‐3‐carboxylic acid) to yield [ 18 F]FFMZ. The synthesis of [ 18 F]FFMZ allows for the production of up to 7 GBq of this PET‐tracer, enough to serve several patients. [ 18 F]FFMZ synthesis was completed in less than 80 min and the radiochemical purity exceeded 98%. Copyright © 2003 John Wiley & Sons, Ltd.