Bibliographic Details
| Title: |
Structure–Activity Relationship Studies of Pyridine-Based Ligands and Identification of a Fluorinated Derivative for Positron Emission Tomography Imaging of Cannabinoid Type 2 Receptors |
| Authors: |
Haider, Achi, Kretz, Julian, Gobbi, Luca, Ahmed, Hazem, Atz, Kenneth, Bürkler, Markus, Bartelmus, Christian, Fingerle, Jürgen, Guba, Wolfgang, Ullmer, Christoph, Honer, Michael, Knuesel, Irene, Weber, Markus, Brink, Andreas, Herde, Adrienne Müller, Keller, Claudia, Schibli, Roger, Mu, Linjing, Grether, Uwe, Ametamey, Simon M. |
| Source: |
Journal of Medicinal Chemistry; December 2019, Vol. 62 Issue: 24 p11165-11181, 17p |
| Abstract: |
The cannabinoid type 2 (CB2) receptor has emerged as a valuable target for therapy and imaging of immune-mediated pathologies. With the aim to find a suitable radiofluorinated analogue of the previously reported CB2 positron emission tomography (PET) radioligand [11C]RSR-056, 38 fluorinated derivatives were synthesized and tested by in vitro binding assays. With a Ki(hCB2) of 6 nM and a selectivity factor of nearly 700 over cannabinoid type 1 receptors, target compound 3exhibited optimal in vitro properties and was selected for evaluation as a PET radioligand. [18F]3was obtained in an average radiochemical yield of 11 ± 4% and molar activities between 33 and 114 GBq/μmol. Specific binding of [18F]3to CB2 was demonstrated by in vitro autoradiography and in vivo PET experiments using the CB2 ligand GW-405 833. Metabolite analysis revealed only intact [18F]3in the rat brain. [18F]3detected CB2 upregulation in human amyotrophic lateral sclerosis spinal cord tissue and may thus become a candidate for diagnostic use in humans. |
| Database: |
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