New imaging technique could catch cancer early, Stanford study finds

STANFORD, Calif. - Nanotechnology is the key to a new, noninvasive biomedical imaging technique that could detect early stages of cancer. The method holds promise for determining not just where tumors are located but also for monitoring their treatment, said scientists at the Stanford University School of Medicine who demonstrated the new approach in mice.

"This imaging modality allows us to see things we've never been able to see before," said Adam de la Zerda, a doctoral student in electrical engineering who was the primary author of a study describing the findings. De la Zerda works in the laboratory of Sanjiv Sam Gambhir, MD, PhD, professor of radiology and director of the Molecular Imaging Program at Stanford, who is the study's senior author. The paper describing their new findings appeared in the Aug. 17 online versioni of Nature Nanotechnology.

The researchers used "smart" targeted carbon nanotubes to home in on cancer cells in living mice. Once the nanotubes zeroed in, laser scans of the animals were done. The nanotubes absorbed the laser energy and released ultrasound waves that pinpointed tumor cell locations.

The novel technique, known as photoacoustic molecular imaging, is faster and less expensive than a magnetic resonance imaging scan, the researchers said, and, unlike a PET-CT scan, requires no ionizing radiation. It can peer into the body to a depth of approximately 5 centimeters (2 inches), making it useful for looking at tissues such as the breast or prostate gland. The scanners could also be adapted to endoscopes, enabling views of internal organs such as the liver. The method is also sensitive enough to pick up tiny, early tumors that can't be seen any other way.

Photoacoustic imaging has been in development for about 10 years, but has been hard to harness for medical applications because it doesn't distinguish well between healthy tissues and those in the early stages of disease. The new study used a targeted imaging agent that enabled a much more powerful technique of photoacoustic molecular imaging, Gambhir said.

In the study, nanotubes were injected in mice as a contrast agent. The tiny nanotubes, made of a black, coal-like material, are so small that 500 of them would have to be lined up end-to-end to reach the thickness of a human hair. They're coated with molecules that bind to a protein secreted by growing tumors. This coating gets the nanotubes to the right location. Then, their carbon cores show up in the photoacoustic molecular imaging scans.

The technology takes advantage of the "photoacoustic effect," a physical phenomenon in which light hits an object and is converted into sound. Shining light on an object heats it up, de la Zerda explained.

"Think of a black car parked in the sun," he said. The car warms up, and the metal expands. Later, the cooling, shrinking metal makes little "tink" sounds.

Carbon nanotubes absorb light even better than a black car, as they are some of the blackest materials ever made. And, when they're hit with a specially tuned pulse of light, the nanotubes release a type of sound wave that's already exploited in medical images.

"We shine light on a nanotube and listen to the ultrasound waves coming out of it," de la Zerda said.

The research team used nanotubes that bound to a protein secreted by tumors to prompt growth of new blood vessels. The nanotubes clustered at new, tumor-feeding blood vessels, revealing tumors' locations and molecular characteristics. The team scanned for artificially induced tumors in mice to show the new method gave a tumor-specific view. Animals without tumors quickly cleared the nanotubes from their blood, producing blank scan images.

In the future, the nanotube coating could easily be changed to help physicians get useful diagnostic information about a tumor, de la Zerda said. For instance, nanotubes could be coated with molecules that would tell a doctor which anti-cancer drugs would work on a breast tumor. Nanotechnology is being put to work to develop more sensitive imaging agents for use with photoacoustic molecular imaging, as well as different strategies to home in on cancer cells, Gambhir said.

"We will be able to ask a tumor: are you responding to chemotherapy or not?" de la Zerda said. "This should give us early information long before the tumor shrinks or grows."

A companion pilot study in mice, published by Gambhir's team in Nature Nanotechnology in April, suggested the carbon nanotubes are safe to inject. Further safety and efficacy testing will be required before the technique can be tested in humans.

"For decades, we have been able to make images of anatomy," de la Zerda said. "But seeing anatomy and seeing the molecular characteristics of tissue are completely different. With this technique, we can see not just symptoms of disease; we're truly seeing the actual disease."

Gambhir and de la Zerda collaborated with a multidisciplinary team of 13 other Stanford scientists in the Schools of Medicine, Humanities & Sciences, and Engineering, including the laboratories of Butrus Khuri-Yakub, PhD, professor of electrical engineering; Hongjie Dai, PhD, the J.G. Jackson and C.J. Wood Professor of Chemistry at Stanford, and Xiaoyuan Chen, PhD, associate professor of radiology. The research was supported by a Center for Cancer Nanotechnology Excellence U54 grant from the National Cancer Institute and by the nonprofit Canary Foundation.



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