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Picture Perfect

New imaging technique stands to improve research of childhood musculoskeletal cancers

May 2006

by Will Sansom

New imaging technique stands to improve research of childhood musculoskeletal cancers
Blood vessels (red) clearly stand out from the skeleton (white) in this enhanced micro-CT image of a normal living mouse. The work of Dr. Charles Keller and his colleagues will enable scientists to study tumor blood vessel networks in unprecedented detail.
The year was 1973, and the place was Massachusetts. In one of the most public cases ever of a child with cancer, it was announced that 12-year-old Teddy Kennedy, son of U.S. Sen. Edward M. Kennedy, had lost part of his right leg to osteosarcoma. His chance of long-term survival was thought to be on the order of 15 percent. The nation watched through the years, and Edward Kennedy Jr. survived. Today he is an attorney and advocate on behalf of people with disabilities. But unlike Mr. Kennedy, at least one-third of young people do not survive tumors arising in bone or surrounding muscle. New therapies are needed for these aggressive, untreatable cases that take so many young lives.

The mission of the Childrenís Cancer Research Institute (CCRI) at the Health Science Center is precisely aligned with this imperative need to develop more effective and better targeted treatment of childhood cancer, providing models that may benefit persons of all ages with cancer. CCRI Director Sharon B. Murphy, M.D., recognizes the importance of incorporating mouse models of cancer and powerful new techniques of research imaging into the CCRIís arsenal, and she was pleased to be able to recruit Charles Keller, M.D., from the University of Utah in early 2005. "Charles is an outstanding physician-scientist with specialized experience in genetics, pediatric oncology, engineering and small-animal imaging, and he is poised to make major contributions to the field," Dr. Murphy said.

Dr. Keller, assistant professor at the CCRI, aims to improve treatment of alveolar rhabdomyosarcomas Ė cancers that emanate from muscle surrounding bone, generally during adolescence. Dr. Keller and colleagues at the CCRI and the University of Utahís Scientific Computing and Imaging Institute are especially interested in cancer-related angiogenesis, a process in which tumors form blood vessel networks to feed themselves. "We have developed tools that for the first time allow us to analyze tumor vascular beds," Dr. Keller said. "We can therefore monitor the effects of treatment on an alveolar rhabdomyosarcoma mouse model we developed," Dr. Keller said. "Itís been virtually impossible to correctly image live blood vessels at such high resolution before."

The scientists have dramatically increased the usefulness of an imaging technique called micro-CT imaging. The team of cell biologists, computer scientists and engineers has captured never-before-seen views of mouse blood vessels. They did it by using contrast agents Ė dyes that make the blood vessels and soft tissue features stand out from bone Ė and by generating algorithms to more effectively translate biologically significant data into meaningful graphic representations.

Distinguishing blood vessels from bone is nearly impossible using conventional CT scans, which measure material density. Dr. Keller and his Utah collaborators devised a new visualization measure, degree of "edge sharpness," that composes images by including calculations of boneís more distinct boundaries. The result is a much clearer picture of angiogenesis. "If a research team wants to test an agent that blocks angiogenesis, the effectiveness of that agent can be studied in living mice through our imaging techniques," Dr. Keller said. This work was published in a recent issue of the journal Molecular Imaging.

"Dr. Kellerís pioneering work has tremendous potential for improving the way we evaluate novel cancer therapeutic agents that target the tumor vasculature," said Chris H. Takimoto, M.D., Ph.D., director of pharmacology and the Zachry Chair for Translational Research at the Cancer Therapy and Research Centerís Institute for Drug Development. "The level of detail that can be achieved in whole animals using these new imaging techniques is phenomenal. We are tremendously excited to be collaborating with Dr. Kellerís group to bring these state-of-the-art technologies to the field of anti-cancer drug development."

In other work at the CCRI, Dr. Keller studies a genetically programmed mouse model for medulloblastoma, a malignant tumor that starts in the lower portion of the brain and can spread to the spine and other areas. Formation and development of this tumor cannot be imaged with current micro-CT techniques. "It is a tough nut to crack," Dr. Keller said. Fortunately, across the street from the CCRI, the Health Science Centerís Research Imaging Center is aggressively seeking to acquire a multimillion-dollar, state-of-the-art MRI scanner to expand the research studies to these tumors and other brain diseases.

Dr. Keller is supported by grants from the National Cancer Institute and the Sarcoma Foundation of America. He and a colleague have founded a company called Numira Biosciences to patent and commercialize discoveries from his laboratory. The research undoubtedly will help patients who, like the young Teddy Kennedy did 33 years ago, face a life-and-death struggle with cancer. The efforts should lead to understandings that enable more young people, like Mr. Kennedy, to survive well into adulthood after beating muscle and bone cancers.

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