title: Synthesis and preliminary in vitro biological evaluation of new carbon-11-labeled celecoxib derivatives as candidate PET tracers for imaging of COX-2 expression in cancer.
abstract: The enzyme cyclooxygenase-2 (COX-2) is overexpressed in a variety of malignant tumors. This study was designed to develop new radiotracers for imaging of COX-2 in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled celecoxib derivatives, [(11)C]4a-c and [(11)C]8a-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 52 ± 2% (n = 5) and 57 ± 3% (n = 5) radiochemical yields based on [(11)C]CO(2) and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5). The IC(50) values to block COX-2 for known compounds celecoxib (4d), 4a and 4c were 40, 290 and 8 nM, respectively, and preliminary findings from in vitro biological assay indicated that the synthesized new compounds 4b and 8a-d display similar strong inhibitory effectiveness in the MDA-MB-435 human cancer cell line in comparison with the parent compound 4d. These results encourage further in vivo evaluation of carbon-11-labeled celecoxib derivatives as new potential PET radiotracers for imaging of COX-2 expression in cancer.
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.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Miller
authors.forename: Qi-Huang
authors.initials: QH
authors.lastname: Zheng
mesh_terms: D002250:Carbon Radioisotopes; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D002250:Carbon Radioisotopes; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib