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

Recently, two fluorine‐18 labelled derivatives of flumazenil were described: 5‐(2′‐¹⁸F]fluoroethyl)‐5‐desmethylflumazenil (ethyl 8‐fluoro‐5‐¹⁸F]fluoroethyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐f]imidazo1,5‐a] 1,4]diazepine‐3‐carboxylate; ¹⁸F]FEFMZ) and 3‐(2′‐¹⁸F]fluoro)‐flumazenil (2′‐¹⁸F]fluoroethyl 8‐fluoro‐5‐methyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐f]imidazo1,5‐a]‐1,4]diazepine‐3‐carbo‐ xylate; ¹⁸F]FFMZ). Since the biodistribution data of the latter were superior to those of the former we developed a synthetic approach for ¹⁸F]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, ¹⁸F]fluoride was reacted with 2‐bromoethyl triflate using the kryptofix/acetonitrile method to yield 2‐bromo‐¹⁸F]fluoroethane (¹⁸F]BFE). In the second step, distilled ¹⁸F]BFE was reacted with the tetrabutylammonium salt of 3‐desethylflumazenil (8‐fluoro‐5‐methyl‐6‐oxo‐5,6‐dihydro‐4H‐benzo‐f]imidazo1,5‐a] 1,4]diazepine‐3‐carboxylic acid) to yield ¹⁸F]FFMZ. The synthesis of ¹⁸F]FFMZ allows for the production of up to 7 GBq of this PET‐tracer, enough to serve several patients. ¹⁸F]FFMZ synthesis was completed in less than 80 min and the radiochemical purity exceeded 98%. Copyright © 2003 John Wiley & Sons, Ltd.