title: 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.
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, L3-208, Indianapolis, IN 46202, USA.
authors.forename: Mingzhang
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, L3-208, Indianapolis, IN 46202, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Miller
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, L3-208, Indianapolis, IN 46202, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hutchins
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, L3-208, Indianapolis, IN 46202, USA.
authors.forename: Qi-Huang
authors.initials: QH
authors.lastname: Zheng
mesh_terms: D001665:Binding Sites; D002250:Carbon Radioisotopes / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D007553:Isotope Labeling; D008024:Ligands; D057054:Molecular Imaging / Q000379:methods; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay / Q000379:methods*; D043884:Receptor, Cannabinoid, CB1 / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D052616:Solid Phase Extraction; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D002250:Carbon Radioisotopes; D008024:Ligands; D011804:Quinolines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2