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Fluorescent Compounds Make Tumors Glow
Detecting Tumors Earlier
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A series of novel imaging agents could light up tumors as they begin to form - before they turn deadly - and signal their transition to aggressive cancers. The compounds - fluorescent inhibitors of the enzyme cyclooxygenase-2 (COX-2) - could have broad applications for detecting tumors earlier, monitoring a tumor's transition from pre-malignancy to more aggressive growth, and defining tumor margins during surgical removal. COX-2 is an attractive target for molecular imaging. It's not found in most normal tissues, and then it is "turned on" in inflammatory lesions and tumors.
Lawrence Marnett, Ph.D., the leader of the Vanderbilt University team that developed the compounds, which are described in the May 1 issue of Cancer Research, and his colleagues previously demonstrated that fluorescent COX-2 inhibitors - which they have now dubbed "fluorocoxibs" - were useful probes for protein binding, but their early molecules were not appropriate for cellular or in vivo imaging. In studies led by senior research specialist Brenda Crews, the investigators evaluated the potential of these compounds for in vivo imaging using three different animal models: irritant-induced inflammation in the mouse foot pad; human tumors grafted into mice; and spontaneous tumors in mice. In each case, the two fluorocoxibs - injected intravenously or into the abdominal cavity - accumulated in the inflamed or tumor tissue, giving it a fluorescent "glow."
To move the agents toward human clinical trials, the team will conduct additional toxicology and pharmacology testing and develop the tools for particular settings that are amenable to fluorescence imaging, such as skin or sites accessible by endoscope. In the esophagus, for example, a pre-malignant lesion called Barrett's esophagus can transition to a low-grade dysplasia, then to a high-grade dysplasia, and finally to malignant cancer, which has a one-year survival of only 10 percent. For a patient with Barrett's esophagus, detecting the transition to dysplasia is critical. The problem is that dysplasia is not visibly different from the pre-malignant Barrett's lesion, so physicians collect random biopsy samples - which might miss areas of dysplasia.
Original Publication:
Uddin J.
Imaging & Microscopy Issue 4 as free epaper or pdf download
Md., et al.: Selective Visualization of Cyclooxygenase-2 in Inflammation and Cancer by Targeted Fluorescent Imaging Agents. Cancer Research 70, 3618, May 1, 2010. doi: 10.1158/0008-5472.CAN-09-2664 (2010) American Association for Cancer Research
Authors:
Craig Boerner
Keywords: COX-2 Enzyme Cyclooxygenase-2 Fluorescence Imaging Tumor Vanderbilt University medical Center
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