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A ¹⁸F-labeled fluorobutyl-substituted spirocyclic piperidine derivative as a selective radioligand for PET Imaging of sigma₁ receptors.

Authors: Aurélie, Maisonial; Eva, Grosse Maestrup; Steffen, Fischer; Achim, Hiller; Matthias, Scheunemann; Christian, Wiese; Dirk, Schepmann; +4 Authors

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.

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Keywords

Fluorine Radioisotopes, Brain, Mice, Piperidines, Isotope Labeling, Positron-Emission Tomography, Animals, Autoradiography, Haloperidol, Receptors, sigma, Female, Spiro Compounds, Tissue Distribution, Radiopharmaceuticals

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
24
Average
Top 10%
Top 10%
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