Molecular detectives being developed to prowl the body snooping out diseases

Cover story in Science looks at imaging technique that uses the latest semiconductor materials

Sam Gambhir

Advances in the material used to make semiconductor chips have opened the door to a new era in medical imaging that will allow doctors to pinpoint diseases with greater precision than ever before.

The cover story of this week’s issue of Science highlights this direction in nanotechnology that relies on a recent technique known as quantum dots, or qdots. These are tiny, nanocrystal structures made from the latest semiconductor materials. They can be injected into animals to produce high-resolution multi-colored images of individual molecules moving within the animals’ cells for an extended period of time.

“Qdots are the perfect merger of nanotechnology with molecular imaging,” said Sanjiv Sam Gambhir, the head of the School of Medicine’s molecular imaging program and a co-author of the review. “Our article paints a picture for how nanotechnology will be used initially in animals and soon humans to image molecular and cellular events.”

Gambhir, MD, PhD, wrote the article with several colleagues from UCLA, where he had worked until 2003 when he joined the Stanford faculty. In the year and a half he has been here, he has been figuring out how to use qdots and other surveillance molecules that he calls “molecular detectives.” Like Sherlock Holmes or Hercule Poirot, these particles scope out mysteries and report back to the authorities what they find—but the molecular detectives are doing their investigations inside a body.

Among Gambhir’s detectives the qdots are particularly promising. Fabricated from semiconductor materials, they are like tiny droplets of free electrons and are capable of fluorescence when stimulated with the right light energy. As a result, they can be engineered for high-resolution imaging that can allow scientists to see events as intricate and minute as individual molecules moving within cells.

According to the article, qdots are typically a few nanometers in diameter—roughly a billionth of a meter. They are larger than many molecules but much smaller than cells. The structures are created in nanofabrication facilities where they can be designed to function with virtually unlimited visualization prop erties. Stanford has such facilities in the materials science department, and there are companies that are beginning to sell qdots.

Gambhir, a professor of radiology and head of the division of nuclear medicine, said that the application of this new tool from the world of electronic materials science to biological uses would allow new and better ways to diagnose and treat cancer and other diseases. The story in Science notes, for instance, that qdots have been designed with pieces of protein attached to them that allowed them to zero in and latch on to the distinctive proteins on certain cancer cells.

And the paper also reports that an advantage of qdots is that they can be constructed to emit a specific color of light when stimulated.

“What this technology allows that can’t be done now is multiplexing—having signals of different colors letting us image many things simultaneously,” said Gambhir. The problem with most imaging strategies right now, he added, is that only one probe can be injected at a time, giving one signal at a time.

“If I want to know 30 things about a cancer at once, I would have to inject one probe then wait for the answer from that one. Then inject another probe and wait. And so on,” he said. “The multiple signals of qdot technology are like having a colorful barcode.”

Different colored qdots could generate a kind of optical barcode reflecting the levels of various tumor markers. The barcode could indicate tumor type and stage. The diagnosis would not require any tissue removal, as the detection process would be done either externally or through a small inserted catheter.

Real-time imaging during surgery is also a definite possibility using qdots, said Gambhir. “Surgeons will begin surgery, turn the lights off, shine a light and see all the glowing areas inside the body,” he said. The diagnosis and any needed surgery would be done while the patient is on the operating table, he added.

In the future, Gambhir said he could also imagine that someone with suspected breast cancer would get a qdot scan instead of getting a mammogram. Injected qdots would wander around the body, home in on the breast cancer and then would light up the cancer cells when stimulated by external light.

“This way is vastly more sensitive than anything we have now,” he said. “We could detect far, far fewer cells because the qdots have locked onto the cancer cells and are producing light showing us where the cancer is.” And as you treat the person with surgery or drugs, the process could be repeated to ensure that the treatment was successful.

Gambhir, investigators in the chemistry and materials science departments at Stanford and his UCLA collaborators are in the process of applying for a $25 million grant from the National Cancer Institute to explore the use of qdots in diagnosis and treating cancer.

“Now is the time that we can realistically start to engineer nanoparticles that will improve therapies and how we detect cancer,” he said. “This isn’t just science fiction.”