title: A ¹⁸F-labeled fluorobutyl-substituted spirocyclic piperidine derivative as a selective radioligand for PET Imaging of sigma₁ receptors.
abstract: In this study, we synthesized and evaluated a new spirocyclic piperidine derivative 3, containing a 4-fluorobutyl side chain, as a PET radioligand for neuroimaging of σ₁ receptors. In vitro, compound 3 displayed high affinity for σ₁ receptors (K(i) =1.2 nM) as well as high selectivity. [¹⁸F]3 radiosynthesis was performed from the corresponding tosylate precursor, with high radiochemical yield (45-51 %), purity (>98 %), and specific activity (>201 GBq μmol⁻¹). Metabolic stability of [¹⁸F]3 in the brain of CD-1 mice was verified, and no penetration of peripheral radiometabolites into the cerebral tissue was observed. Results of ex vivo autoradiography revealed that the distribution of [¹⁸F]3 in the brain corresponded to regions with high σ₁ receptor density. The highest region-specific total-to-nonspecific ratio was determined in the facial nucleus (4.00). Biodistribution studies indicated rapid and high levels in brain uptake of [¹⁸F]3 (2.2 % ID per gram at 5 min p.i.). Pre-administration of haloperidol significantly inhibited [¹⁸F]3 uptake into the brain and σ₁ receptor-expressing organs, further confirming in vivo target specificity.
authors: Helmholtz-Zentrum Dresden-Rossendorf, Research site Leipzig, Institute of Radiopharmacy, Permoserstraße 15, 04318 Leipzig, Germany. a.maisonial@hzdr.de
authors: Aurélie
authors: A
authors: Maisonial
authors: Eva
authors: E
authors: Grosse Maestrup
authors: Steffen
authors: S
authors: Fischer
authors: Achim
authors: A
authors: Hiller
authors: Matthias
authors: M
authors: Scheunemann
authors: Christian
authors: C
authors: Wiese
authors: Dirk
authors: D
authors: Schepmann
authors: Jörg
authors: J
authors: Steinbach
authors: Winnie
authors: W
authors: Deuther-Conrad
authors: Bernhard
authors: B
authors: Wünsch
authors: Peter
authors: P
authors: Brust