10 Emerging Technologies That Will Change the World

TECHNOLOGY REVIEW

February 2003

Molecular Imaging

At Massachusetts General Hospital's Center for Molecular Imaging Research-a bustling facility nestled next to an old Navy shipyard-Umar Mahmood uses a digital camera to peer through the skin of a living mouse into a growing tumor. Using fluorescent tags and calibrated filters, the radiologist actually sees the effects of the cancer on a molecular scale: destructive enzymes secreted by the tumor show up on Mahmood's computer screen as splotches of red, yellow, and green. In the future, he says, such "molecular imaging" may lead to earlier detection of human disease, as well as more effective therapies.

Molecular imaging-shorthand for a number of techniques that let researchers watch genes, proteins, and other molecules at work in the body-has exploded, thanks to advances in cell biology, biochemical agents, and computer analysis. Research groups around the world are joining the effort to use magnetic, nuclear, and optical imaging techniques to study the molecular interactions that underlie biological processes. Unlike x-ray, ultrasound, and other conventional techniques that give doctors only such anatomical clues as the size of a tumor, molecular imaging could help track the underlying causes of disease. The appearance of an unusual protein in a cluster of cells, say, might signal the onset of cancer. Mahmood is helping to lead the effort to put the technology into medical practice.

It is challenging, though, to detect a particular molecule in the midst of cellular activity. When researchers inject a tag that binds to the molecule, they face the problem of distinguishing the bound tags from the extra, unbound tags. So Mahmood has worked with chemists to develop "smart probes" that change their brightness or their magnetic properties when they meet their target. "This is a big deal," says David Piwnica-Worms, director of the Molecular Imaging Center at Washington University in St. Louis. The method, he explains, "allows you to see selected proteins and enzymes that you might miss with standard tracer techniques."

In a series of groundbreaking experiments, Mahmood's team treated cancerous mice with a drug meant to block the production of an enzyme that promotes tumor growth. The researchers then injected fluorescent probes designed to light up in the presence of that enzyme. Under an optical scanner, treated tumors showed up as less fluorescent than untreated tumors, demonstrating the potential of molecular imaging to monitor treatments in real time-rather than waiting months to see whether a tumor shrinks. "The big goal is to select the optimum therapy for a patient and then to check that, say, a drug is hitting a particular receptor," says John Hoffman, director of the Molecular Imaging Program at the National Cancer Institute. What's more, molecular imaging could be used to detect cancer signals that precede anatomical changes by months or years, eliminating the need for surgeons to cut out a piece of tissue to make a diagnosis. "At the end of the day, we may replace a number of biopsies with imaging," Mahmood says.

In Mahmood's lab, clinical trials are under way for magnetic resonance imaging of blood vessel growth-an early indicator of tumor growth and other changes. For more advanced techniques such as those used in the mouse cancer study, clinical trials are two years away. The big picture: 10 years down the road, molecular imaging may take the place of mammograms, biopsies, and other diagnostic techniques. Although it won't replace conventional imaging entirely, says Mahmood, molecular imaging will have a profound effect both on basic medical research and on high-end patient care. Indeed, as his work next door to the shipyard makes clear, an important new field of biotechnology has set sail. -Gregory T. Huang

Others in 
MOLECULAR IMAGING RESEARCHER PROJECT Ronald Blasberg 
Memorial Sloan-Kettering Cancer Center Imaging of gene expression Harvey Herschman 
U. California, Los Angeles Tracking of gene therapy, gene activities David Piwnica-Worms 
Washington U. Protein interactions, imaging tools Patricia Price 
U. Manchester Clinical oncology, imaging drug targets Ralph Weissleder 
Harvard Medical School Cell tracking, molecular targets, drug discovery