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Synthesis and in vitro biological evaluation of carbon-11-labeled quinoline derivatives as new candidate PET radioligands for cannabinoid CB2 receptor imaging.

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.
AuthorsMingzhang Gao, Min Wang, Kathy D Miller, Gary D Hutchins, Qi-Huang Zheng
JournalBioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 18 Issue 6 Pg. 2099-2106 (Mar 15 2010) ISSN: 1464-3391 [Electronic] England
PMID20189815 (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.)
CopyrightCopyright 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Carbon Radioisotopes
  • Ligands
  • Quinolines
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
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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