PET Probes Provide Clues into Immune Cellular Function

In addition to revealing the extent and cellular composition of an immune response, the probes also may be useful in evaluating therapies that target different cellular components of the immune system, according to Dr. Owen Witte, a UCLA professor of microbiology, immunology, and molecular genetics, and senior author of the study.

"We demonstrated with this study that each probe targets different cells in the immune system with a high degree of specificity,” said Dr. Witte, director of the UCLA Broad Stem Cell Research Center. "When cells are activated to do their job as an immune cell, the FDG probe is good at recognizing the subset of activated macrophages, while the FAC probe is good at recognizing the activated lymphocytes, as well as the macrophages. When tested sequentially, the combined information from the scans using the two probes gives you a better status of immune response.”

The study, with lead author Evan Nair-Gill, a student in the campus' Medical Scientist Training Program, was conducted on mice bearing virally induced sarcomas. The article was published May 18, 2010, in the early online edition of the Journal of Clinical Investigation. Testing the probes in humans is the next step.

The scans provide insights into how the immune system works, for example, in response to cancer or autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis, according to Dr. Witte. They also could be used to see how therapies, such as vaccines and monoclonal antibodies meant to stimulate an immune response, are functioning within the body of a patient. "This could give us another way to measure the efficacy of certain drugs,” Dr. Witte said. "With some drugs, you could measure a change in the immune response within a week.”

If the drugs are working, physicians could stay the course. If they are not working or not working well enough, the therapy could be discontinued, sparing the patient a months-long exposure to an ineffective drug. The next step will be evaluating the two probes in humans with a range of diseases, including cancer and autoimmune disorders, to confirm the work.

Dr. Witte and his colleagues licensed the FAC probe to Sofie Biosciences (Culver City, CA, USA; www.sofie-biosciences.com), which is owned in part by Dr. Witte and other UCLA faculty members. Researchers created the small molecule by slightly altering the molecular structure of one of the most commonly used chemotherapy drugs, gemcitabine. They then added a radiolabel so the cells that take in the probe can be seen during PET scanning.

The probe measures the activity of an essential cell biochemical pathway called the DNA salvage pathway, which acts as a recycling mechanism that helps with DNA replication and repair. All cells use this biochemical pathway to different levels. However, in lymphocytes and macrophages that are proliferating during an immune response, the pathway is activated to very high levels. Because of that, the probe accumulates at high levels in those cells, reported Dr. Witte.

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