Bringing new images to light

A child with brain cancer has a good chance for survival if his or her cancer is completely removed by surgery. But that is far from an easy task for a surgeon operating on certain types of brain tumors that can be difficult to distinguish from healthy brain tissue.

"In some parts of the brain, it's impossible to tell where the cancer starts and ends because the normal brain cells look identical to the tumor cells," said Dr. Jim Olson, a pediatric cancer specialist and an investigator in the Clinical Research Division. "A surgeon doesn't want to leave any cancer cells behind — but there can be serious consequences if healthy brain tissue is removed."

A new research project in Olson's lab is literally bringing those tumor cells to light, making it easier to spot them and more precisely eliminate them. Olson and his colleagues at the University of Washington are using a technique they call tumor painting to tag tumor cells in mice with a dye that shines brightly when exposed to particular wavelengths of light. They hope this will provide surgeons with an additional tool to help them precisely remove tumors from the brain. Once they complete testing of tumor painting in mice, they plan to take the procedure directly to clinical trials with brain-cancer patients.

Tumor painting is one of several innovative projects under way at the center made possible by new body-imaging techniques that allow scientists to see tumors inside living mice. Development of a new shared resource for small-animal imaging was initiated late last year to address the growing research needs for such technology. Imaging methods such as computed tomography (CT) scanning and magnetic resonance imaging (MRI) scaled for use with mice are now available to center researchers.

When combined with molecular approaches for targeting cancer genes and proteins, mouse imaging becomes an important proving ground for the development of new diagnostic tests and treatments, which must be tested in mice before they can be made available to people with cancer and other diseases. In the process, investigators also will learn much about the basic biology of cancer and other illnesses.

Hastening discoveries

"What imaging lets us do is hasten the pace of scientific discovery," said Dr. Norm Greenberg, a Clinical Research Division investigator who uses imaging to study prostate cancer in mice. "We'd like to be able to do in the research lab what we can do in the clinic — which will speed the development of new ways to diagnose and treat disease more effectively."

Two imaging machines recently installed at the center are beginning to make these goals possible for Fred Hutchinson investigators. One instrument, a GE Micro CT scanner, images live mice or other small animals as well as small samples of tissue. CT scanners use a type of x-ray equipment to obtain image data from different angles around the body, and reconstruct these images to show a cross-section of body tissues and organs. A second instrument, the Xenogen IVIS imaging system, allows researchers to light up tissues or cells in mice that have been engineered to contain proteins tagged with light-emitting or fluorescent molecules.

In addition, center researchers have access to an MRI machine through a collaboration with UW. A second machine soon will be installed at UW's South Lake Union facility. Plans are also under way at UW to acquire a positron emission tomography (PET) scanner for use with small animals, an instrument that can measure metabolic activity of a tumor using tracer molecules that instantly reveal whether a tumor is growing or shrinking in response to treatment.

The availability of this technology has sparked the interest of more than 100 investigators at both institutions, as demonstrated by attendance at an imaging workshop organized by Greenberg and colleagues last November. One result of the workshop is a monthly seminar and informal discussion session at Fred Hutchinson, designed to foster collaboration between imaging experts and basic and clinical lab investigators.

A noninvasive tool

Cancer researchers are eager to develop imaging-based cancer-detection tests for two key reasons: they are noninvasive and can provide doctors with detailed disease information much faster than many conventional methods. As center scientists work toward the goal of earlier diagnosis of cancer using blood tests that can spot proteins released by tumors, these advantages have become increasingly apparent, Greenberg said.

"Let's say a blood test tells a doctor a patient has cancer," he said. "Where is the tumor? Is it growing? Does it need to be removed or can it just be monitored for a time? Imaging can help us answer those questions by allowing us to see tumors inside the living body and get information about them without resorting to surgery."

Even when tumors are smaller than the head of a pin and long before they cause symptoms, scientists may be able to spot them using imaging coupled with injected tracer molecules that hone in on cancer cells and light them up with dyes or radioactivity that has been linked to the tracer. For example, imaging can be used to spot the earliest signs that a cancer has spread, or metastasized, from the site of the original tumor to distant parts of the body. Dr. Pete Nelson, an investigator in the Clinical Research and Human Biology divisions, plans to use this approach with mice in order to understand how aggressive prostate tumors spread to the bone or other tissues.

"We also would like to use imaging to clearly see different parts of a tumor, which may have very different properties," Nelson said. "This will help us to learn which types of cells contribute to the development of aggressive disease, which will ultimately help us to detect it earlier and treat it more effectively."

Faster results

One of the most exciting advances in imaging technology is the potential to determine whether a cancer treatment is working in days rather than months, Olson said.

"Currently, when we try a type of chemotherapy in a cancer patient, we typically treat for three months and then perform a CT or MRI scan to see whether the tumor is shrinking," he said. "But if a treatment is not working, three months is a long time to wait. We're working on better imaging methods mice to allow us to evaluate within 72 hours of administering treatment whether the cancer cells are dying."

To measure the extent of cell death caused by chemotherapy, Olson, Dr. Miqin Zhang in UW's Material Sciences and Engineering Department and Dr. Ray Sze in the UW/Children's Hospital and Regional Medical Center Radiology Department have taken a protein that binds to dying cells and linked it to a particle that can be detected with an imaging scanner. They are developing a similar approach to detect changes in brain tissue in patients with Huntington disease, an inherited degenerative nervous-system disease.

Variations on this approach can even be used to treat cancer, Olson said. For example, particles coupled with proteins that target cancer can also be engineered as drug-delivery vehicles.

Not surprisingly, a single scientist is rarely skilled in all of the scientific fields required to take such projects from beginning to end, Greenberg said.

"Imaging is a real convergence of technology, involving chemistry, physics, biology and radiology," he said. "That's why we are putting effort into providing as many opportunities for collaboration as we can."

Coffee, tea or MRI?

Imaging Cafés are informal meetings of Fred Hutchinson and University of Washington investigators who have interest or expertise in imaging. Cafés meet from 5 to 6 p.m on the first Monday of each month in room B1-072/074. For more information, visit the center's imaging Web site at http://imaging.fhcrc.org.

More information about the developing small-animal imaging shared resource will be provided to center investigators in early spring.