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Synthesis and evaluation of a 18F-labeled 4-phenylpiperidine-4-carbonitrile radioligand for σ1 receptor imaging.
- Source :
- Journal of Labelled Compounds & Radiopharmaceuticals; Jul2016, Vol. 59 Issue 9, p332-339, 8p
- Publication Year :
- 2016
-
Abstract
- We report the design and synthesis of several 4-phenylpiperidine-4-carbonitrile derivatives as σ<subscript>1</subscript> receptor ligands. In vitro radioligand competition binding assays showed that all the ligands exhibited low nanomolar affinity for σ<subscript>1</subscript> receptors ( K<subscript>i</subscript>(σ<subscript>1</subscript>) = 1.22-2.14 nM) and extremely high subtype selectivity ( K<subscript>i</subscript>(σ<subscript>2</subscript>) = 830-1710 nM; K<subscript>i</subscript>(σ<subscript>2</subscript>)/ K<subscript>i</subscript>(σ<subscript>1</subscript>) = 680-887). [<superscript>18</superscript>F]9 was prepared in 42-46% isolated radiochemical yield, with a radiochemical purity of >99% by HPLC analysis after purification, via nucleophilic <superscript>18</superscript>F<superscript>-</superscript> substitution of the corresponding tosylate precursor. Biodistribution studies in mice demonstrated high initial brain uptakes and high brain-to-blood ratios. Administration of SA4503 or haloperidol 5 min prior to injection of [<superscript>18</superscript>F]9 significantly reduced the accumulation of radiotracers in organs known to contain σ<subscript>1</subscript> receptors. Two radioactive metabolites were observed in the brain at 30 min after radiotracer injection. [<superscript>18</superscript>F]9 may serve as a lead compound to develop suitable radiotracers for σ<subscript>1</subscript> receptor imaging with positron emission tomography. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03624803
- Volume :
- 59
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Journal of Labelled Compounds & Radiopharmaceuticals
- Publication Type :
- Academic Journal
- Accession number :
- 116620022
- Full Text :
- https://doi.org/10.1002/jlcr.3408