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Updated: Jun 13, 2026
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
Selective visualization of cyclooxygenase-2 in inflammation and cancer by targeted fluorescent imaging agents
Md Jashim Uddin1, Brenda C Crews, Anna L Blobaum
1AB Hancock, Jr Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
Abstract:
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.
Insights
Novel fluorescence imaging agents targeting cyclooxygenase-2 (COX-2) enable precise detection of inflammation and cancer. These agents show high specificity and contrast, ideal for early-stage disease diagnosis.
Area of Science:
- Biomedical imaging
- Molecular imaging
- Cancer diagnostics
Background:
- Molecular imaging faces challenges in differentiating inflammation and cancer due to non-specific contrast agent accumulation in normal tissues.
- Cyclooxygenase-2 (COX-2) is a key biomarker, overexpressed in inflammatory lesions and various cancers, but absent in healthy cells.
Purpose of the Study:
- To develop novel fluorescence imaging agents with high specificity for cyclooxygenase-2 (COX-2).
- To evaluate the efficacy of these agents in detecting inflammation and COX-2-expressing tumors in vivo.
Main Methods:
- Synthesis and characterization of novel fluorescence imaging agents targeting COX-2.
- In vivo fluorescence imaging studies in animal models following i.p. or i.v. administration.
- Confirmation of COX-2 specificity using genetic knockout models and active site inhibition.
Main Results:
- The novel agents demonstrated high enrichment in inflamed or tumor tissues compared to normal tissues.
- Sufficient signal was generated for effective in vivo fluorescence imaging.
- COX-2-specific delivery was confirmed through genetic and pharmacological blocking studies.
- Only the intact parent compound was detected at the target site.
Conclusions:
- The developed fluorocoxibs exhibit high specificity, contrast, and detectability for COX-2.
- These agents are promising tools for the early detection of inflammatory conditions and COX-2-expressing cancers, including esophageal, oropharyngeal, and colon cancers.
