November 2004

Molecular Imaging Resources

Molecular imaging anchors NCI nanotech alliance

By: Laura Lane

The National Cancer Institute plans to focus its nanotechnology research on the key areas of molecular imaging, including the creation of imaging agents with unparalleled specificity and sensitivity. Speaking at the launch of the NCI's Cancer Nanotechnology Alliance in September, experts in the field and regulatory and governmental officials outlined the components of a plan designed to improve detection and treatment of cancer and, ultimately, prevent cancer from occurring at all.

Exploring the capabilities of nanotechnology and harnessing them can lead to diagnostic tools to quickly sift through the 30,000 proteins of the human proteome, spotting those that have gone awry in specific tissues. This would allow for affordable, efficient detection of cancer, according to Nobel Laureate Richard Smalley, Ph.D., a professor of chemistry at Rice University in Houston.

"Nanotech is really the only hope to do that," he said.

The NCI plans to focus on six areas:

- molecular imaging and early detection;

- in vivo imaging;

- assessment of treatment efficacy with molecular reporters;

- multifunctional therapeutics;

- prevention and control of cancer; and

- technologies and solutions to enable research.

Facilitating progress will be the NCI's infrastructure of 61 cancer centers across the country and its network of researchers. Both have been growing and maturing since the passage of the National Cancer Act in 1971, said NCI director Dr. Andrew von Eschenbach.

"The NCI is uniquely positioned with infrastructure and momentum to work cooperatively and collaboratively toward fully expressing technology and transforming nanotechnology, creating a world in which no one suffers and dies as a result of cancer," he said.

The initiative's emphasis on translation research to create clinically viable applications distinguishes it from a widely publicized project put forth by National Institutes of Health. NIH director Dr. Elias Zerhouni's road map focuses on opportunities associated with basic research. The road map's goal of funding nanotechnology research and its role in examining biological processes will help, however, to boost the efforts of the NCI, which is allocating $144.3 million for the alliance during the course of five years.

MULTIDISCIPLINARY APPROACH

Nanotechnology involves the use of cellular and molecular components and engineered materials-typically clusters of atoms, molecules, and molecular fragments-at the most elemental level of biology, according to NCI officials. These components, referred to as nanoparticles, are compounds, including several types of imaging contrast agents, that are 10 to 100 nanometers in diameter. Identifying the best candidates to fight cancer will require the collaboration of physical scientists, biologists, radiologists, and other researchers, according to Philip J. Bond, undersecretary of commerce for technology.

Program organizers will form five Centers of Cancer Nanotechnology Excellence that will integrate nanotechnology development into basic and clinical cancer research. The centers will work with affiliated research centers in engineering and physical sciences. The alliance will also fund multidisciplinary research teams and individual projects as well as the development of the Nanotechnology Characterization Laboratory, which will serve as the unifying force, interacting with everyone involved in the alliance.

Researchers are already finding success in developing nanoparticles that can be used as imaging agents that circulate through the blood and bind only to the specific target or molecule, said, Mauro Ferrari, a professor of biomedical engineering and medicine at Ohio State University. One such nanoparticle is the nanoshell composed of a silica core and a metallic surface that can be activated externally. This nanoshell is being designed not only for optimal specificity, but also as a therapeutic agent. It can be activated with local radiation that will direct therapy to diseased tissue only, sparing the surrounding healthy tissue.

Researchers can attach common contrast agents such as gadolinium and use current imaging techniques to observe malignant tissue and make diagnoses, said Samuel E. Wickline, Ph.D., a professor of medicine at Washington University in St. Louis. Wickline's research has focused on imaging angiogenesis in mice and developing nanoparticles that will serve as both an imaging agent and a delivery vehicle for drugs (see cover story).

Advances in imaging agents will also make it possible for physicians to track the efficacy of treatments more conveniently, von Eschenbach said.

"The implication is that we'll be providing the right treatment to the right patients at the right time," he said.

Nanostructures such as cantilever beams and nanowire sensors will also play a large role in the early detection of disease and in gauging therapeutic efficacy, Ferrari said. Cantilever beams, which act as microelectronic mechanical systems on the nanoscale, can detect the tiny forces that occur with binding events. The beams and the nanowire sensors can be used to detect the presence of certain proteins and/or quantify amounts that may indicate disease.