The disadvantages of Raman spectroscopy include poor tissue penetration, similar to the problems encountered during infrared optical imaging. Targeted Raman particles involve a complex of gold atoms producing a much larger molecule than most radiopharmaceuticals, Gambhir said. Penetrating the blood-brain barrier and the interiors of larger tumors may be difficult.

For its initial experiments, the Stanford group adapted a Raman microscope for small-animal imaging. Each Raman particle can be aimed at a specific cell surface receptor, protein, enzyme, or other organic chemical. The return signal can be tuned to a specific radiofrequency to allow multiplexing.

The Stanford group favors a point-by-point raster data acquisition technique capable of submillimeter spatial resolution. The temporal resolution is about 30 minutes for whole-body mouse imaging. With additional improvements, the procedure will be performed in about 90 seconds, Gambhir said.

The Stanford group is with working with the FDA to rapidly move Raman particle imaging into the clinical arena. With the help of a National Cancer Institute grant, they are building a Raman endoscope for colorectal applications.

Gambhir and colleagues envision spraying the wall of the colon with targeted Raman particles. These would latch onto cancer cells and could help expose hard-to-detect flat polyps.

The endoscopic approach potentially addresses the inherent tissue penetration problem. Toxicity is less of a concern for the FDA when the agent is released and quickly ejected from the bowel, Gambhir said.

Multiplexing would help boost diagnostic accuracy, Gambhir said. Instead of targeting only carcinoembryonic antigen on the cancer cell surfaces, the application can simultaneously target epidermal growth factor receptor on the cells.

“If you then aim your gold nanoparticles at third and fourth targets, the detection of the disease becomes increasingly specific,” Gambhir said.