The most widely used molecular imaging technique in the lab is fluorescence. What makes Raman spectroscopy unique is that “you get a very sharp signal back, unlike [with] fluorescence, where you get a broad spectrum of energy,” Gambhir says.
Claudio Vinegoni, an imaging specialist at the Center for Molecular Imaging Research at Harvard and at the Massachusetts General Hospital, who was not involved in the study, says that although scientists can use fluorescent molecules of different colors to see more than one molecule at a time, the ability to multiplex is limited because their signals quickly begin to overlap. In contrast, with Raman spectroscopy, “every molecule has its own Raman spectrum,” Vinegoni says, so there is no possibility of the signals interfering. Because of their specificity, Raman nanoparticles can also be imaged at concentrations a thousand times lower than what can be detected using fluorescent quantum dots.
Although Raman spectroscopy could prove immediately useful in animal imaging, Gambhir ultimately hopes to bring it into the clinic. The best method for imaging biochemical events in humans is through PET imaging, in which a radioactive tracer injected into the body makes it possible to detect chemical activity. Gambhir’s goal is to “develop the next generation of imaging technologies that wouldn’t have to use radioactivity.” In addition to its ability to image many things at once, Raman spectroscopy offers better sensitivity than PET and would be much less expensive.
One of the major shortcomings of this technique, as in all optical imaging methods, is the limited ability of light to penetrate deep into tissue. Although it can be used to visualize the internal organs of a mouse, Gambhir says that in humans, the technique would be more useful for visualizing tumors close to the surface of the skin, such as melanomas or even breast cancer. The technique could also be used in conjunction with endoscopes that probe inside the body. Gambhir’s team is planning a clinical trial to test the use of Raman particles in conjunction with colonoscopies for detecting early-stage cancers. In this procedure, the nanoparticles could simply be sprayed onto the surface of the colon rather than injected into the body. But a key challenge for bringing this technique into the clinic will be determining the safety of nanoparticles as probes–studies that Gambhir’s group is currently undertaking.