Tondera Christoph, Ullm Sandra, Laube Markus, Meister Sebastian, Neuber Christin, Mosch Birgit, Kniess Torsten, Pietzsch Jens
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.
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany.
Biochem Biophys Res Commun. 2015 Feb 27;458(1):40-5. doi: 10.1016/j.bbrc.2015.01.057. Epub 2015 Jan 27.
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.
本研究旨在通过光学成像，利用一类具有自荧光的2,3-二芳基取代吲哚基选择性环氧化酶-2（COX-2）抑制剂（2,3-二芳基吲哚型昔布类）的代表性化合物，在体内对COX-2进行可视化。通过2-[4-(氨基磺酰基)phenyl]-3-(4-甲氧基苯基)-1H-吲哚（C1），在佛波醇肉豆蔻酸酯（TPA）诱导炎症的小鼠模型或携带人黑色素瘤细胞异种移植瘤的小鼠模型中成功实现了COX-2的可视化。通过免疫印迹法证实了TPA诱导的炎症部位和人黑色素瘤异种移植瘤中COX-2蛋白的表达。使用替代标志物、假注射以及不表达COX-2的黑色素瘤细胞进行的对照实验进一步证实了C1与组织结合的特异性。2,3-二芳基吲哚型昔布类药物治疗与诊断特性的融合可能会拓宽COX-2靶向治疗的应用范围，例如用于原位引导手术和离体诊断。
