Imaging agents offer new view of inflammation, cancer

October 7, 2011

A series of novel imaging agents could make it possible to "see" tumors in their earliest stages, before they turn deadly.

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

Vanderbilt University investigators describe the new in a paper featured on the cover of the October issue of .

"This is the first COX-2-targeted PET imaging agent validated for use in animal models of inflammation and cancer," said Lawrence Marnett, Ph.D., director of the Vanderbilt Institute of and leader of the team that developed the compounds.

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, Marnett explained.

"As a tumor grows and becomes increasingly malignant, COX-2 levels go up," Marnett said.

To develop compounds that target COX-2 and can be detected by PET imaging, Jashim Uddin, Ph.D., research assistant professor of Biochemistry, started with the "core" chemical structures of the anti-inflammatory medicines indomethacin and celecoxib and modified them to add the element fluorine in various chemical configurations.

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

The researchers demonstrated the potential of this 18-F compound for in vivo in two animal models: irritant-induced inflammation in the rat footpad and human tumors grafted into mice.

They showed that the 18-F compound accumulated in the inflamed foot, but not the non-inflamed foot, and that pre-treatment of the animals with celecoxib blocked the signal. In mice bearing both COX-2-positive and COX-2-negative human tumors, the 18-F compound accumulated only in the COX-2-positive tumor.

The studies support further development of these agents as probes for early detection of cancer and for evaluation of the COX-2 status of pre-malignant 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," Marnett said.

Explore further: COX-2 inhibitors delay pancreatic cancer precursors in mice

Related Stories

COX-2 inhibitors delay pancreatic cancer precursors in mice

August 1, 2007

Nimesulide, a cyclooxygenase-2 (COX-2) inhibitor, delays the progression of precancerous pancreatic lesions in mice, according to researchers at David Geffen School of Medicine at UCLA. While inflammation has been shown to ...

Study: Celecoxib can cause arrhythmias

January 15, 2008

U.S. medical researchers have determined the anti-inflammatory drug celecoxib (Celebrex) can adversely affect heart rhythm in fruit fly and rat models.

Fluorescent compounds make tumors glow

April 29, 2010

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.

Study puts a new spin on ibuprofen's actions

September 25, 2011

Ibuprofen, naproxen, and related non-steroidal anti-inflammatory drugs (NSAIDs) – the subjects of years of study – still have some secrets to reveal about how they work.

Imaging inflammation in the living brain

September 30, 2011

Inflammation occurs in the human brain during illnesses such as Alzheimer's disease, Parkinson’s disease, stroke and traumatic brain injury. Now, a research team in Japan has developed a probe that can bind to the pro-inflammatory ...

Recommended for you

Proton pump found to regulate blood pH in stingrays

August 19, 2016

Researchers at Scripps Institution of Oceanography at the University of California San Diego have discovered the same enzyme used by "boneworms" to dissolve whale carcasses, and that helps promote photosynthesis in corals, ...

Uncovering a new pathway to halting metastasis

August 19, 2016

Metastasis, the process by which cancer cells leave the primary tumor and spread to other sites in the body, is responsible for more than 90 percent of cancer deaths. Thus, there is a significant need to improve the therapeutic ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.