title: Targeted imaging of cancer by fluorocoxib C, a near-infrared cyclooxygenase-2 probe.
abstract: Cyclooxygenase-2 (COX-2) is a promising target for the imaging of cancer in a range of diagnostic and therapeutic settings. We report a near-infrared COX-2-targeted probe, fluorocoxib C (FC), for visualization of solid tumors by optical imaging. FC exhibits selective and potent COX-2 inhibition in both purified protein and human cancercell lines. In vivo optical imaging shows selective accumulation of FC in COX-2-overexpressing human tumor xenografts [1483 head and neck squamous cell carcinoma (HNSCC)] implanted in nude mice, while minimal uptake is detectable in COX-2-negative tumor xenografts (HCT116)or 1483 HNSCC xenografts preblocked with the COX-2-selective inhibitor celecoxib. Time course imaging studies conducted from 3 h to 7-day post-FC injection revealed a marked reduction in nonspecific fluorescent signals with retention of fluorescence in 1483 HNSCC tumors. Thus, use of FC in a delayed imaging protocol offers an approach to improve imaging signal-to-noise that should improve cancer detection in multiple preclinical and clinical settings.
authors.forename: Md Jashim
authors.initials: MJ
authors.lastname: Uddin
authors.forename: Brenda C
authors.initials: BC
authors.lastname: Crews
authors.forename: Kebreab
authors.initials: K
authors.lastname: Ghebreselasie
authors.forename: Cristina K
authors.initials: CK
authors.lastname: Daniel
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kingsley
authors.forename: Shu
authors.initials: S
authors.lastname: Xu
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D007089:Image Enhancement / Q000379:methods; D007259:Infrared Rays; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D025202:Molecular Diagnostic Techniques / Q000379:methods; D057054:Molecular Imaging / Q000379:methods; D015336:Molecular Probe Techniques; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2