The Duke University bioengineers combined tightly focused heat with optical coherence tomography (OCT), which has often been called the optical equivalent of ultrasound. OCT is commonly used in medical clinics where imaging at the highest resolution is critical, such as in the retina. These experiments represent the first time the technique has been extended to the functional imaging of cells expressing particular molecular receptors.
For their experiments, the Duke team attached nanospheres of gold to a targeting molecule known as a monoclonal antibody. Gold is a metal that not only is an efficient conductor of heat, but whose effects in the body are well known. The antibody they used targets epidermal growth factor receptor (EGFR), a cell-surface receptor implicated in cancer.
These "tagged" antibodies were then applied to the surface of a three-dimensional tissue model composed of human cells – both cancerous and non-cancerous. Skala hoped that these antibodies would home in on cells that were overproducing EGFR on their surfaces, an indicator of cancerous activity. Then the photothermal OCT would be able to detect them by showing where the gold spheres were concentrated.
"When we directed the photothermal OCT at the tissue, we found that the cells that were overexpressing EGFR gave off a signal 300 percent higher than cells with low expressions of EGFR," the researchers said.
Adding heat to this form of microscopy technique created a phenomenon much like that seen on very hot days, when portions of the pavement far in the distance seem to float or hover above the road. As they changed the temperature, the light pathways would change in measurable ways.
In this manner, they explained, they were not only able to "see" cells within the tissue, but they were able to capture the molecular function of an antibody attaching to a receptor.
"The use of metal nanoparticles as contrast agents with photothermal OCT technology could lead to a host of potential clinical applications," they said. "Organically-based contrast agents can cause damage or death to the targeted cells, while metal nanospheres are relatively safer." "Also, given the wide range of nanoparticle shapes and sizes, coupled with the ability to 'tune" the optical wavelength of the OCT, we can customize our approach to many different target types," they added.
Skala plans to expand the use of this approach in animal models to better understand the role of different cancer therapies. Tumors with elevated levels of EGFR are known to have a poor prognosis, and she plans to use photothermal OCT to measure how these tumor types react to different therapies.
COMPAMED.de; Quelle: Duke University