Radiosynthesis of novel 18F-labelled derivatives of indiplon as potential GABAA receptor imaging tracers for PET

✍ Scribed by Steffen Fischer; Achim Hiller; Matthias Scheunemann; Winnie Deuther-Conrad; Alexander Hoepping; Michael Diekers; Florian Wegner; Peter Brust; Jörg Steinbach

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: French
• Weight: 246 KB
• Volume: 51
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1473

✦ Synopsis

Abstract

The involvement of gamma amino butyric acid (GABA) receptors in a variety of neurological and psychiatric diseases has promoted the development and use of radiolabelled benzodiazepines (BZ) for brain imaging by PET. However, these radioligands are unable to distinguish between the various subtypes of GABA~A~ receptors. Novel non‐BZ such as the pyrazolo‐pyrimidine indiplon proved to be selective for the α~1~‐subunit of the GABA~A~ receptor. Here, we describe the syntheses of four novel ^18^F‐labelled indiplon derivatives. Radiosyntheses were performed via n.c.a. ^18^F‐nucleophilic substitution starting from the tosyl, bromo, and 4‐nitrobenzoyl precursors to obtain fluorine substituted N‐alkylamide side chain derivatives of indiplon, followed by multistep purification using semi‐preparative high‐performance liquid chromatography and solid phase extraction. Tosyl and bromo precursors were converted into ^18^F‐labelled indiplon derivatives with good and reproducible radiochemical yield (RCY) (35–70%, decay corrected), high radiochemical purity (≥98.5%), and high specific activity ( > 150 GBq/µmol). By contrast, a low RCY (5–10%) and specific activity (10–15 GBq/µmol) were achieved for the 4‐nitrobenzoyl precursor. Copyright © 2008 John Wiley & Sons, Ltd.