08/20/08

 

BY ERIN DIGITALE

	Sam Gambhir

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 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 and primary author of the study reporting the findings. De la Zerda works in the lab of Sanjiv Sam Gambhir, MD, PhD, professor of radiology who directs the Molecular Imaging Program at Stanford and is the study's senior author. Their findings appeared online Aug. 17 in 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 about 2 inches, useful for seeing a breast or prostate gland. It can be adapted to endoscopes to view internal organs and can pick up tiny early tumors not seen any other way.

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

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

This 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. When hit with a specialized pulse of light, they release a type of sound wave 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 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 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. Nanotubes coated with molecules would tell a doctor which anti-cancer drugs would work on a breast tumor. Nanotechnology could develop more sensitive imaging agents for 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. More testing is required before the technique can be tried in humans.

"For decades, we have been able to make images of anatomy," said de la Zerda. "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 seeing the actual disease."

Gambhir and de la Zerda collaborated with 13 other Stanford scientists in the Schools of Medicine, Humanities & Sciences and Engineering, including the labs 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 grant from the National Cancer Institute and by the nonprofit Canary Foundation.

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Erin Digitale is a science-writing intern in the Office of Communication & Public Affairs.