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

✍ Scribed by Wolfgang Wadsak; Markus Mitterhauser; Leonhard-Key Mien; Stefan Tögel; Bernhard Keppler; Robert Dudczak; Kurt Kletter

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: French
• Weight: 152 KB
• Volume: 46
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.783

✦ Synopsis

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.