Selective visualization of cyclooxygenase-2 in inflammation and cancer by targeted fluorescent imaging agents.

Uddin MJ, Crews BC, Blobaum AL, Kingsley PJ, Gorden DL, McIntyre JO, Matrisian LM, Subbaramaiah K, Dannenberg AJ, Piston DW, Marnett LJ
Cancer Res. 2010 70 (9): 3618-27

PMID: 20430759 · PMCID: PMC2864539 · DOI:10.1158/0008-5472.CAN-09-2664

Effective diagnosis of inflammation and cancer by molecular imaging is challenging because of interference from nonselective accumulation of the contrast agents in normal tissues. Here, we report a series of novel fluorescence imaging agents that efficiently target cyclooxygenase-2 (COX-2), which is normally absent from cells, but is found at high levels in inflammatory lesions and in many premalignant and malignant tumors. After either i.p. or i.v. injection, these reagents become highly enriched in inflamed or tumor tissue compared with normal tissue and this accumulation provides sufficient signal for in vivo fluorescence imaging. Further, we show that only the intact parent compound is found in the region of interest. COX-2-specific delivery was unambiguously confirmed using animals bearing targeted deletions of COX-2 and by blocking the COX-2 active site with high-affinity inhibitors in both in vitro and in vivo models. Because of their high specificity, contrast, and detectability, these fluorocoxibs are ideal candidates for detection of inflammatory lesions or early-stage COX-2-expressing human cancers, such as those in the esophagus, oropharynx, and colon.

(c)2010 AACR.

MeSH Terms (18)

Animals Carcinoma, Squamous Cell Carrageenan Colorectal Neoplasms Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Female Fluorescent Dyes HCT116 Cells Head and Neck Neoplasms Humans Inflammation Macrophages Mice Mice, Inbred C57BL Mice, Nude Microscopy, Confocal Molecular Imaging

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