Abstract |
Cannabinoids have been recently proposed as a new family of potential antitumor agents, and cannabinoid receptor 2 (CB2) is believed to be over-expressed in tumor cells. This study was designed to develop new radioligands for imaging of CB2 receptor in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled 2-oxoquinoline and 2-chloroquinoline derivatives, [(11)C]6a-d and [(11)C]9a-d, were prepared by O-[(11)C]methylation of their corresponding precursors using [(11)C]CH(3)OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 40-50% radiochemical yields based on [(11)C]CO(2) and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 15-20 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 111-185 GBq/micromol. Radioligand binding assays indicated compounds 6f, 6b, and 9f display potent in vitro binding affinities with nanomolar K(i) values and at least 100-2000-fold selectivity for CB2.
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Authors | Mingzhang Gao, Min Wang, Kathy D Miller, Gary D Hutchins, Qi-Huang Zheng |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 18
Issue 6
Pg. 2099-2106
(Mar 15 2010)
ISSN: 1464-3391 [Electronic] England |
PMID | 20189815
(Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright 2010 Elsevier Ltd. All rights reserved. |
Chemical References |
- Carbon Radioisotopes
- Ligands
- Quinolines
- Receptor, Cannabinoid, CB1
- Receptor, Cannabinoid, CB2
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Topics |
- Binding Sites
- Carbon Radioisotopes
(chemistry)
- Drug Design
- Humans
- Isotope Labeling
- Ligands
- Molecular Imaging
(methods)
- Molecular Structure
- Positron-Emission Tomography
(methods)
- Quinolines
(chemical synthesis, chemistry, pharmacology)
- Radioligand Assay
(methods)
- Receptor, Cannabinoid, CB1
(analysis, chemistry, metabolism)
- Receptor, Cannabinoid, CB2
(analysis, chemistry, metabolism)
- Solid Phase Extraction
- Stereoisomerism
- Structure-Activity Relationship
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