According to a new study in the Journal of Clinical Investigation, a new PET radiotracer is being developed by researchers. The new PET radiotracer is being designed to latch onto and illuminate immune cells in cancer patients, which can offer an earlier look at treatment response. Currently, tracers such as FDG focus on cancer cells.
T-cells are a type of white blood cell, and the immune-PET tracer is designed to attach to them when they become active and attack cancerous tumors. Physicians will then be able to view the immune-PET tracer’s progress on PET images. Knowing what’s going on inside a cancer patients cells can open up a lot of possibility for them to avoid toxic radiation and chemotherapy.
“With a lot of therapies and diseases, we cannot visualize what is going on deep within the human body. It is not the same thing as taking a CT or MRI scan and utilizing anatomy,” said senior author Dr. Sanjiv “Sam” Gambhir, PhD, radiology department chair at Stanford University. “We need to visualize molecules, and that is what a PET scan does best. By visualizing molecules, we can elucidate the underlying mechanisms of different diseases and different treatments. Otherwise, we are shooting blindly.”
Gambhir has been actively involved in developing and testing novel PET radiopharmaceuticals and immune-PET tracers in order to find out how well they can identify molecules in cancer cells that might prevent a person’s natural immune system from attacking the disease.
Gambhir, along with his colleagues, discussed how immune checkpoint inhibitors have emerged as a promising tool for monitoring cancer treatment in an April 2017 paper. A major stumbling block that comes up in predicting and monitoring response to therapy has been the lack of imaging methods to noninvasively assess immune checkpoint expression.
A collaboration soon happened between Gambhir and a professor of oncology at Stanford, Dr. Ronald Levy. Coincidentally, it just so happened that both doctors were investigating the uses of OX40, a protein that can be activated on T cells.
Both men were looking at different aspects of OX40. Gambhir was investigating the protein’s role as a checkpoint inhibitor and potential biomarker to assess the efficacy of immunotherapy. Dr. Levy, however, was working with OX40 to create a tracer that would activate T cells to attack tumors.
“He wanted to use that target to rev up the immune system,” Gambhir said. “We wanted to use OX40 as a marker for highly activated T cells, so we could predict whether a given therapy would work or monitor whether it is working.”
Levy’s PET tracer features two stimulating agents: The first part coaxes T cells to producing OX40 on the cell surface, while the second binds to OX40 and enables the T cells to interact with tumor cells. As a result, the tracer is able to energize the immune cells to destroy tumors.
How does the PET tracer work inside the human body? Once it’s injected, the tracer immediately seeks out the cancer killing T cells. The tracer then is able to bind itself to the OX40, and the accumulation then glows on PET images which show the T cell activation. If there is little to no such activity on a PET scan, that would indicate that immunotherapy isn’t working for the patient and would mean the treatment should be adjusted or changed altogether.
“It is one way to grade the immunotherapy and look to see if the tumor changes,” Gambhir said. “We can see what the immune cells are doing and whether they are even going to the tumor site so they can destroy the tumor. If not, where are the immune cells going?”
This new use of PET differs from conventional scans with FDG, which is used with tumors.
“Because tumor cells love to eat sugar, they also love to eat FDG,” Gambhir said. “That is what produces a hot signal on a PET scan. On a PET scan with FDG, we are looking at where tumors are, not where the immune cells are. So this new scan is not measuring tumor metabolism with FDG, but is measuring activated T cells in the body. By doing that, we can know much earlier whether someone is responding to immunotherapy.”
If a cancer patient isn’t responding to immunotherapy, it’s best to find out early in order to look at different treatment options.
“If they are not responding, you don’t want to wait months to find out because then we are losing time,” Gambhir said. “A tumor might grow and become more heterogeneous and that much more difficult to treat.”
Immunotherapy’s main objective is to activate T cells and activate them to kill tumors. Immunotherapy can also be advantageous for the patient, as it relies on natural processing within the body. With successful immunotherapy treatments, a patient might avoid having to undergo radiation or chemotherapy.
“[Immunotherapy] potentially would be less toxic in that we don’t have to give all kinds of things that not only hurt tumor cells but also hurt regular cells,” Gambhir said. “The whole idea of immunotherapy is giving something that is less toxic and is not dependent upon some very toxic approach that, unfortunately, hurts the tumor but also the patient.”
Gambhir and his colleagues plan to begin a phase I trial in about four months, in order to see how well the immuno-PET approach works with humans. Currently, they’ve only experimented on mice.
“Just because things work in mice, of course, does not mean they will work in humans. So there’s a big jump now to go to humans,” he said. “This approach of using OX40, which sits on T cells, is a good way of therapeutically approaching cancer and, from an imaging perspective, letting us track these immune cells in a new way.”
Even if the combination of PET, OX40, and tracking activated T cells is not successful for cancer, Gambhir believes the approach may be useful for patients suffering from rheumatoid arthritis and multiple sclerosis.
