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Rewriting Life

A Deeper Look at Disease

A molecular imaging system shows the telltale signs of tumors.

An imaging system developed by a Massachusetts company makes visible the chemical activity of tissues deep inside the body. Researchers are using the system to watch the rise and spread of cancer in mice, and pharmaceutical companies are using it to better determine the effects of new drugs in animals. Made by VisEn Medical of Woburn, the molecular imaging system is allowing researchers to see deeper into the body and look at a wider range of chemical activity than is possible with existing imaging techniques.

Probing disease: A molecular imaging system made by VisEn Medical illuminates the activity of proteins deep inside mice and constructs 3-D images of tumors and other diseased tissue.

Conventional imaging techniques, such as magnetic resonance imaging, give only anatomical information–they allow doctors to see the shape and size of tumors, for example. Researchers hope new molecular imaging technologies that provide information on the activity of tissues, as VisEn’s technology does, will help doctors diagnose diseases earlier, monitor whether treatments are working, and even provide guidance during surgery. (See “Watching Cancer Cells Die” and “Seeing Tumors with Quantum Dots.”)

The VisEn molecular imaging system relies on large fluorescent-protein probes that interact with disease-related proteins in the body and allow researchers to see where they are and in what concentrations. Some of these probe proteins constantly emit fluorescent light. Others, which provide clearer images, don’t emit any light when they’re injected in the body but light up when they are cleaved by specific proteins in the body. One probe protein detects an enzyme that helps tumors “chew up surrounding tissue” so that they can grow and spread, says Jeff Peterson, director of applied biology at VisEn. Other probes include one that detects a protein implicated in the bone changes associated with cancer and arthritis.

By measuring the intensity of fluorescence from the probes, researchers can find disease sites. Each probe fluoresces at a different wavelength, so it’s possible to look for many different kinds of activities at once. For example, a researcher might look for bone-building and tissue-chewing proteins in breast tumors to determine how aggressive they are.

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Because molecular imaging allows researchers to watch tissue activity in real time in live animals, “you can understand earlier if you’re really modifying a disease with a drug,” rather than just controlling symptoms, Peterson points out. He says that a pilot study with a pharmaceutical company demonstrated that for arthritis, imaging inflammatory proteins in live animals works as well as examining tissue from dead animals under the microscope. VisEn is collaborating with Merck, Eli Lilly, and other pharmaceutical companies.

Light from the VisEn probes is captured in pictures taken from multiple angles by a near-infrared camera. These pictures are then mathematically reconstructed into a 3-D image, which is projected for context onto a simple white-light photograph of the animal. Other molecular imaging systems that use fluorescent probes can’t provide 3-D images and can’t penetrate deep into the animal. VisEn’s technology, says Peterson, is most comparable to positron emission tomography (PET). But PET scanning uses radioactive probes, requires a particle accelerator, and can’t measure protein activity level.

Kay Macleod, assistant professor of cancer research at the University of Chicago, is using the probes to study the course of breast cancer in mice. If she were using other imaging methods, says Macleod, she would have to perform surgery on the animals in order to get the laser and camera close enough to the tumors. VisEn’s infrared imaging system reveals tumors deep inside mice, eliminating the need for surgery.

VisEn is applying to the Federal Drug Administration for permission to begin testing the imaging method in humans to look for cancer and atherosclerosis. One challenge is that while the near-infrared light emitted by the probes can pass all the way through mice, it’s absorbed as it passes through humans. Peterson says that the company will develop endoscopes and catheters to bring near-infrared cameras close to human tissues in hopes of guiding surgeons to the ones that are diseased.

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