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Synthesis of fluorinated analogues of sphingosine-1-phosphate antagonists as potential radiotracers for molecular imaging using positron emission tomography.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2014 Oct 01; Vol. 22 (19), pp. 5168-81. Date of Electronic Publication: 2014 Aug 17. - Publication Year :
- 2014
-
Abstract
- Sphingosine-1-phosphate (S1P) receptors play major roles in cardiovascular, immunological and neurological diseases. The recent approval of the sphingolipid drug Fingolimod (Gilenya®), a sphingosine-1-phosphate agonist for relapsing multiple sclerosis, in 2010 exemplifies the potential for targeting sphingolipids for the treatment of human disorders. Moreover, non-invasive in vivo imaging of S1P receptors that are not available till now would contribute to the understanding of their role in specific pathologies and is therefore of preclinical interest. Based on fluorinated analogues of the S1P1 receptor antagonist W146 showing practically equal in vitro potency as the lead structure, the first S1P receptor antagonist [18F]-radiotracer has been synthesized and tested for in vivo imaging of the S1P1 receptor using positron emission tomography (PET). Though the tracer is serum stable, initial in vivo images show fast metabolism and subsequent accumulation of free [18F]fluoride in the bones.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Anilides chemical synthesis
Anilides chemistry
Animals
CHO Cells
Cells, Cultured
Cricetulus
Dose-Response Relationship, Drug
Fluorine Radioisotopes chemistry
Halogenation
Humans
Male
Mice
Mice, Inbred C57BL
Molecular Structure
Organophosphonates chemical synthesis
Organophosphonates chemistry
Radiopharmaceuticals chemical synthesis
Radiopharmaceuticals chemistry
Receptors, Lysosphingolipid biosynthesis
Structure-Activity Relationship
Tissue Distribution
Anilides pharmacology
Molecular Imaging
Organophosphonates pharmacology
Positron-Emission Tomography
Radiopharmaceuticals pharmacology
Receptors, Lysosphingolipid antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 22
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 25216968
- Full Text :
- https://doi.org/10.1016/j.bmc.2014.08.009