Imaging Agents Offer New View of Inflammation and Cancer

The compounds, derived from inhibitors of the enzyme cyclooxygenase-2 (COX-2) and detectable by positron emission tomography (PET) imaging, may have wide applications for cancer detection, diagnosis, and treatment.

Vanderbilt University (Nashville, TN, USA) investigators described the new imaging agents in an article published in the October 2011 issue of the journal Cancer Prevention Research. “This is the first COX-2-targeted PET imaging agent validated for use in animal models of inflammation and cancer,” said Lawrence Marnett, PhD, director of the Vanderbilt Institute of Chemical Biology and leader of the team that developed the compounds.

COX-2 is a promising target for molecular imaging. It is not found in most healthy tissues, and then it is activated in inflammatory lesions and tumors, Dr. Marnett explained. “As a tumor grows and becomes increasingly malignant, COX-2 levels go up,” he said.

To develop compounds that target COX-2 and that can be detected by PET imaging, Jashim Uddin, PhD, research assistant ,professor of biochemistry, began with the basic chemical structures of the anti-inflammatory medicines indomethacin and celecoxib and modified them to add the element fluorine in various chemical arrangements.

After demonstrating that the fluorinated compounds were selective inhibitors of COX-2, the investigators incorporated radioactive fluorine (F-18) into the most promising compound. Intravenous injection of this F-18 compound into animal models provided sufficient signal for PET imaging.

The researchers demonstrated the potential of this F-18 compound for in vivo PET imaging in two animal models: irritant-induced inflammation in the rat footpad and human tumors grafted into mice. They showed that the F-18 compound accumulated in the inflamed foot, but not the noninflamed foot, and that pretreatment of the animals with celecoxib blocked the signal. In mice bearing both COX-2-positive and COX-2-negative human tumors, the F-18 compound accumulated only in the COX-2-positive tumor.

The studies support additional development of these agents as probes for early detection of cancer and for the assessment of the COX-2 status of premalignant and malignant tumors. “Because COX-2 levels increase during cancer progression in virtually all solid tumors, we think these imaging tools will have many, many different applications,” Dr. Marnett concluded.

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