Witte’s team also attached a radiolabel to the probe that, during a PET scan, glows when it enters a cell. The team then tested the probe in mice. Researchers first injected mice with an oncogenic virus, which caused a tumor to develop. This particular tumor is immunogenic, meaning that the immune system easily recognizes it and quickly attacks. After the virus injection, the team then injected the probe and performed PET scans.
“It’s basically like a heat map, and if there’s a lot of immune cells, it’s red; if less, green; and even less, blue,” says Radu. “It looks spectacular. You can see a three-dimensional image of this mouse, and see these draining lymph nodes, which are close to the tumor, and just see them lighting up.”
The team was able to track the immune response as the tumor developed, and it saw that the areas around the tumor lit up the most after 10 to 14 days, a typical length of time in which an immune response can clear an infection.
Radu says that in the future, clinicians may be able to use this new PET probe to image immune responses, in addition to using other techniques, such as CT scans, that can image tumors. In combination, these techniques may enable doctors to watch a tumor shrink as the body’s immune system attacks so that they can determine the effectiveness of different therapies.
Ronald Germain, deputy chief of the immunology laboratory at the National Institute of Allergy and Infectious Diseases, says that while the group’s images are impressive, it is still not completely clear whether cells other than immune cells are being imaged–an effect that could create an imprecise picture.
“It’s not a completely specific probe, so you’re not going to tell what type of cell is present at a site, which can be very important in making a diagnosis going forward,” says Germain. “However, there is a real need to develop ways to assess immune responses without having to do biopsies, and this is one of several approaches that could be used.”
The researchers are now looking to develop a more specific probe, in addition to their general imaging probe. Radu and his colleagues are systematically examining chemical structures to find others that resemble gemcitabine. The team plans to test these compounds against each other to see which may have greater sensitivity and specificity for detecting certain kinds of immune cells.