Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor
Cannabinoid receptor subtype 2 (CB2) has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease. The CB2 receptor is therefore con...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-03-01
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| Series: | Pharmaceuticals |
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| Online Access: | http://www.mdpi.com/1424-8247/7/3/339 |
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| author | Linjing Mu Roger Slavik Adrienne Müller Kasim Popaj Stjepko Čermak Markus Weber Roger Schibli Stefanie D. Krämer Simon M. Ametamey |
| author_facet | Linjing Mu Roger Slavik Adrienne Müller Kasim Popaj Stjepko Čermak Markus Weber Roger Schibli Stefanie D. Krämer Simon M. Ametamey |
| author_sort | Linjing Mu |
| collection | DOAJ |
| description | Cannabinoid receptor subtype 2 (CB2) has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease. The CB2 receptor is therefore considered as a very promising target for therapeutic approaches as well as for imaging. A promising 2-oxoquinoline derivative designated KP23 was synthesized and radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was evaluated. [11C]KP23 was obtained in 10%–25% radiochemical yield (decay corrected) and 99% radiochemical purity. It showed high stability in phosphate buffer, rat and mouse plasma. In vitro autoradiography of rat and mouse spleen slices, as spleen expresses a high physiological expression of CB2 receptors, demonstrated that [11C]KP23 exhibits specific binding towards CB2. High spleen uptake of [11C]KP23 was observed in dynamic in vivo PET studies with Wistar rats. In conclusion, [11C]KP23 showed promising in vitro and in vivo characteristics. Further evaluation with diseased animal model which has higher CB2 expression levels in the brain is warranted. |
| first_indexed | 2024-12-12T06:39:43Z |
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| id | doaj.art-3b270f1cbe444995a658b5b0e7972f23 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-12-12T06:39:43Z |
| publishDate | 2014-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-3b270f1cbe444995a658b5b0e7972f232022-12-22T00:34:23ZengMDPI AGPharmaceuticals1424-82472014-03-017333935210.3390/ph7030339ph7030339Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 ReceptorLinjing Mu0Roger Slavik1Adrienne Müller2Kasim Popaj3Stjepko Čermak4Markus Weber5Roger Schibli6Stefanie D. Krämer7Simon M. Ametamey8Center for Radiopharmaceutical Sciences of ETH-PSI-USZ, Department of Nuclear Medicine, University Hospital Zürich, CH-8091 Zürich, SwitzerlandCenter for Radiopharmaceutical Sciences of ETH-PSI-USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zürich, SwitzerlandCenter for Radiopharmaceutical Sciences of ETH-PSI-USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zürich, SwitzerlandCenter for Radiopharmaceutical Sciences of ETH-PSI-USZ, Department of Nuclear Medicine, University Hospital Zürich, CH-8091 Zürich, SwitzerlandCenter for Radiopharmaceutical Sciences of ETH-PSI-USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zürich, SwitzerlandNeuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, CH-9007 St. Gallen, SwitzerlandCenter for Radiopharmaceutical Sciences of ETH-PSI-USZ, Department of Nuclear Medicine, University Hospital Zürich, CH-8091 Zürich, SwitzerlandCenter for Radiopharmaceutical Sciences of ETH-PSI-USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zürich, SwitzerlandCenter for Radiopharmaceutical Sciences of ETH-PSI-USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zürich, SwitzerlandCannabinoid receptor subtype 2 (CB2) has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease. The CB2 receptor is therefore considered as a very promising target for therapeutic approaches as well as for imaging. A promising 2-oxoquinoline derivative designated KP23 was synthesized and radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was evaluated. [11C]KP23 was obtained in 10%–25% radiochemical yield (decay corrected) and 99% radiochemical purity. It showed high stability in phosphate buffer, rat and mouse plasma. In vitro autoradiography of rat and mouse spleen slices, as spleen expresses a high physiological expression of CB2 receptors, demonstrated that [11C]KP23 exhibits specific binding towards CB2. High spleen uptake of [11C]KP23 was observed in dynamic in vivo PET studies with Wistar rats. In conclusion, [11C]KP23 showed promising in vitro and in vivo characteristics. Further evaluation with diseased animal model which has higher CB2 expression levels in the brain is warranted.http://www.mdpi.com/1424-8247/7/3/339cannabinoid receptor type 2 ligandCB2 receptorneurodegenerationradiolabelingautoradiographysmall-animal PET |
| spellingShingle | Linjing Mu Roger Slavik Adrienne Müller Kasim Popaj Stjepko Čermak Markus Weber Roger Schibli Stefanie D. Krämer Simon M. Ametamey Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor Pharmaceuticals cannabinoid receptor type 2 ligand CB2 receptor neurodegeneration radiolabeling autoradiography small-animal PET |
| title | Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor |
| title_full | Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor |
| title_fullStr | Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor |
| title_full_unstemmed | Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor |
| title_short | Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor |
| title_sort | synthesis and preliminary evaluation of a 2 oxoquinoline carboxylic acid derivative for pet imaging the cannabinoid type 2 receptor |
| topic | cannabinoid receptor type 2 ligand CB2 receptor neurodegeneration radiolabeling autoradiography small-animal PET |
| url | http://www.mdpi.com/1424-8247/7/3/339 |
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