Tiny Q-dots may enable more precise brain surgery

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Darrell Sapp, Post-Gazette
Dr. Marcel Bruchez holds up a solution of nanoparticles, which emit infrared light, in his lab at Mellon Institute. He is working to develop quantum dots, or Q-dots, for use in imaging difficult brain cancers.
Click photo for larger image.

Imaging is an important tool in modern medicine, but capturing brain cancer on film poses a particular challenge.

The major problem lies in distinguishing cancer from healthy tissue in neural and brain cancers known as gliomas.

Enter Marcel P. Bruchez, a Carnegie Mellon University associate research professor in chemistry and his amazing quantum dots.

Q-dots, as they are called, are nanometer-sized crystallized particles with semiconductor properties. Distinct sizes of Q-dots have unique optical properties, Dr. Bruchez said, and they can be designed to emit specific wavelengths of light.

To capture the image of a Q-dot with infrared cameras, Dr. Bruchez designed a Q-dot that emits infrared wavelengths.

The next big question was how to get Q-dots inside brain tumors, and only brain tumors, so they can be photographed. That's where white blood cells, or macrophages, which are the soldiers of the immune system, emerged as ideal Q-dot taxis to the brain.

When Q-dots are introduced into the bloodstream, macrophages engulf the microscopic aliens but cannot digest them, as would happen with biological invaders.

Macrophages, with their Q-dot payload, travel bodywide and congregate wherever infection or inflammation is, as is their mission. For that reason, once they are inside the brain, they gather inside the tumors and leave healthy tissue alone.

In that sense, Q-dot-spiked macrophages target the cancer: "Brain cancer actively recruits them," Dr. Bruchez said.

With a large enough dose, the Q-dots outline the tumor, allowing an infrared camera to snap images that reveal tumor size, shape and location. Such images could help guide neurosurgeons in the process of removing the tumors.

Better imaging techniques allow surgeons to remove larger portions or entire tumors with less peripheral damage to healthy brain tissue.

To date, the project has been successful in imaging tumors in animals -- rats in particular.

Dr. Bruchez continues working with Dr. Steven A. Toms, a neurosurgeon in the Cleveland Clinic's Neural Science Institute and director of a section in the brain tumor and neuro-oncology center, among others, to refine the procedure. The March edition of Neurosurgery published their most recent success in imaging tumors in animals.

The eventual step is to proceed to human studies, but that will require a few more tweaks and turns.

Dr. Toms praised Dr. Bruchez as "extraordinarily bright and a real superstar" in his field. He said he figured out how to make nanoparticles that not only glow in the dark but also are water soluble.

He said such particles can be used to help surgeons find the general location of brain tumors. Surgeons then can use fiber optics to guide them during the surgery to the precise location.

Once the area is reached, the surgeon can actually see the area of the tumor because it will be deep red. "Shine a blue light and when you take out the red, then the tumor is gone. It's like the television commercial, 'Get the red out.' "

He said the process also could work for other tumors and inflammation bodywide. The optical equipment would cost $10,000 to $50,000 -- rather than MRI imaging that now must be used for brain cancer, which can cost well into the millions.

"It's a straightforward concept," he said. "Surgeons are optical creatures. We like to look at things."

For now, the Q-dots being used are made of cadmium, a dangerous heavy metal. Dr. Bruchez said he is busy developing a safer Q-dot that emits the same infrared wavelengths. Dr. Toms said Dr. Bruchez is working to make nontoxic Q-dots from bismuth, a heavy metal.

"We have work in progress," Dr. Bruchez said, noting plans soon to publish details about the new Q-dot. Still, he said, the team is years away from using it in people. "Safety and efficacy issues have to be addressed," he said.

The project marks the latest in a growing list of accomplishments for Dr. Bruchez, 33.

As a graduate student, he modified Q-dots so they could be used to tag proteins and label cells. Based on that work, he started Quantum Dot Corp. in Hayward, Calif., to develop and sell the dots for biological applications.

In 2005, Invitrogen Corp. purchased the corporation, and he soon after joined CMU's Molecular Biosensor and Imaging Center and became program manager for the National Technology Center for Networks and Pathways.

He holds 16 patents and has received prestigious awards for his work, including Massachusetts Institute of Technology's TR100 in 2004, which recognizes 100 innovators under 35 who are transforming technology.

In 2003, the magazine Science recognized his development of Q-dots for biological purposes as one of the Top 10 scientific innovations that year.

"I am excited about the ultimate application of these materials," Dr. Bruchez said.

Darrell Sapp, Post-Gazette
Dr. Marcel Bruchez's Q-dots are made of cadmium, a dangerous heavy metal. He is working to develop nontoxic Q-dots from bismuth, but says the team is years away from using it in people.
Click photo for larger image.

David Templeton can be reached at dtempleton@post-gazette.com or 412-263-1578.


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