title: Optical imaging of COX-2: studies on an autofluorescent 2,3-diaryl-substituted indole-based cyclooxygenase-2 inhibitor.
abstract: This study aimed at in vivo visualization of cyclooxygenase-2 (COX-2) by optical imaging using a representative compound of a class of autofluorescent 2,3-diaryl-substituted indole-based selective COX-2 inhibitors (2,3-diaryl-indole coxibs). COX-2 was successfully visualized in mice models with phorbol myristate ester (TPA)-induced inflammation or bearing xenografted human melanoma cells by 2-[4-(aminosulfonyl)phenyl]-3-(4-methoxyphenyl)-1H-indole (C1). COX-2 protein expression in both TPA-induced inflammatory sites and human melanoma xenografts was confirmed by immunoblotting. Control experiments using surrogate markers, sham injections, and non-COX-2 expressing melanoma cells further confirmed specificity of tissue association of C1. The merging of therapeutic and diagnostic properties of 2,3-diaryl-indole coxibs may widen the range of applications of COX-2-targeted treatment, e.g., for in situ-guided surgery and ex vivo diagnostics.
authors: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany; Technische Universität Dresden, Department of Chemistry and Food Chemistry, Dresden, Germany.
authors: Christoph
authors: C
authors: Tondera
authors: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany; Technische Universität Dresden, Department of Chemistry and Food Chemistry, Dresden, Germany.
authors: Sandra
authors: S
authors: Ullm
authors: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany; Technische Universität Dresden, Department of Chemistry and Food Chemistry, Dresden, Germany.
authors: Markus
authors: M
authors: Laube
authors: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany.
authors: Sebastian
authors: S
authors: Meister
authors: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany.
authors: Christin
authors: C
authors: Neuber
authors: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany.
authors: Birgit
authors: B
authors: Mosch
authors: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany.
authors: Torsten
authors: T
authors: Kniess
authors: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany; Technische Universität Dresden, Department of Chemistry and Food Chemistry, Dresden, Germany. Electronic address: j.pietzsch@hzdr.de.
authors: Jens
authors: J
authors: Pietzsch
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000032:analysis* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D064593:Heterografts; D006801:Humans; D007211:Indoles / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008545:Melanoma / Q000201:enzymology / Q000473:pathology; D008815:Mice, Inbred Strains; D015335:Molecular Probes / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D061848:Optical Imaging / Q000379:methods*; D013449:Sulfonamides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: C000597479:2-(4-(aminosulfonyl)phenyl)-3-(4-methoxyphenyl)-1H-indole; D052246:Cyclooxygenase 2 Inhibitors; D007211:Indoles; D015335:Molecular Probes; D013449:Sulfonamides; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D013755:Tetradecanoylphorbol Acetate
keywords: Fluorescence; Luminescence; Melanoma-associated inflammation; Phorbol myristate ester-induced COX-2 expression; Rodent melanoma xenograft model