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Archive - Oct 7, 2011

New Imaging Agents May Enable Early Visualization of Cancer

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 cancer detection, diagnosis, and treatment. Vanderbilt University investigators describe the new imaging agents in a paper featured on the cover of the October 2011 issue of Cancer Prevention Research. "This is the first COX-2-targeted PET imaging agent validated for use in animal models of inflammation and cancer," said Dr. Lawrence Marnett, director of the Vanderbilt Institute of Chemical Biology 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, Dr. Marnett explained. "As a tumor grows and becomes increasingly malignant, COX-2 levels go up," Dr. Marnett said. To develop compounds that target COX-2 and can be detected by PET imaging, Dr. Jashim Uddin, 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. Intravenous injection 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 PET imaging in two animal models: irritant-induced inflammation in the rat footpad and human tumors grafted into mice.

Potential New Targets for Treatment of Inflammatory and Autoimmune Diseases

Researchers have discovered a cellular pathway that promotes inflammation in diseases like asthma, rheumatoid arthritis, psoriasis, inflammatory bowel disease, and multiple sclerosis. Understanding the details of this pathway may provide opportunities for tailored treatments of inflammatory and autoimmune diseases. Discovery of this pathway was the work of an active collaboration between Dr. Xiaoxia Li and Dr. Thomas Hamilton, Department Chair, both of the Department of Immunology at Lerner Research Institute of the Cleveland Clinic. Their two publications in the September 2011 issue of Nature Immunology, selected for a News and Views article in the same issue, portray how a protein molecule known as interleukin-17 (IL-17) spurs inflammation by recruiting specific white blood cells to sites of infection and injury, producing a strong, pathogenic response. Being able to block this pathway may allow treatment of IL-17-induced inflammatory diseases. Molecular factors discovered by Drs. Li and Hamilton make this concept a potential strategy. "We are excited by the possibilities that this new research opens up for developing improved therapeutics for these difficult diseases," Dr. Hamilton said. "Being able to collaborate like this really expedites the science," Dr. Li added, "ultimately leading, we hope, to profound improvement for those suffering from these autoimmune and inflammatory conditions." [Press release] [Nature Immunology abstract 1] [Nature Immunology abstract 2] [Nature Immunology News & Views article]

Study Confirms Genetic Link to Suicidal Behavior

A new study from the Centre for Addiction and Mental Health in Canada has found evidence that a specific gene is linked to suicidal behaviour, adding to our knowledge of the many complex causes of suicide. This research may help doctors one day target the gene in prevention efforts. In the past, studies have implicated the gene for brain-derived neurotrophic factor (BDNF) in suicidal behaviour. BDNF is involved in the development of the nervous system. After pooling results from eleven previous studies and adding their own study data involving people with schizophrenia, CAMH scientists confirmed that among people with a psychiatric diagnosis, those with the methionine ("met") variation of the BDNF gene had a higher risk of suicidal behavior compared to those with the valine variation. The review, published online on August 30, 2011 in the International Journal of Neuropsychopharmacology, included data from 3,352 people, of whom 1,202 had a history of suicidal behavior. The news coincides with Mental Illness Awareness Week, October 2-8, and World Mental Health Day, October 10. "Our findings may lead to the testing and development of treatments that target this gene in order to help prevent suicide," says Dr. James Kennedy, director of CAMH's Neuroscience Research Department. "In the future, if other researchers can replicate and extend our findings, then genetic testing may be possible to help identify people at increased risk for suicide." As the low-functioning BDNF met variation is a risk factor for suicidal behavior, it may also be possible to develop a compound to increase BDNF functioning, Dr. Kennedy says. About 90 percent of people who have died by suicide had at least one mental health disorder, the researchers note.