JCI: PET probes have different cell specificities during immune response

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The commonly used PET probe, FDG and a new probe developed by researchers at University of California, Los Angeles (UCLA), 18F-FAC reveal different functions in diverse cells of the immune system, providing a non-invasive and much clearer picture of an immune response in action, according to an article published May 17 in the early online edition of the Journal of Clinical Investigation.

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, said Owen N. Witte, MD, professor of microbiology, immunology and molecular genetics at the UCLA, a Howard Hughes Medical Institute investigator and senior author of the study.

In the study, lead author Evan Nair-Gill, PhD student in Medical Scientist Training Program at UCLA and colleagues investigated the immune cell specificity of PET probes on mice bearing virally-induced sarcomas for two different metabolic pathways : [18F]–2-fluorodeoxyglucose ([18F]-FDG) for glycolysis, and [18F]–2-fluoro-d-(arabinofuranosyl)cytosine ([18F]-FAC) for deoxycytidine salvage.

“We demonstrated with this study that each probe targets different cells in the immune system with a high degree of specificity,” said Witte. “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.”

This could give us another way to measure the efficacy of certain drugs,” Witte added. “With some drugs, you could measure a change in the immune response within a week.”

The next step will be testing the two probes in humans with a range of diseases, including cancer and auto-immune disorders, to confirm the work.

The scans provide clues to how the immune system works, for example, in response to cancer or auto-immune diseases such as rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis, Witte said. 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.

Witte and his colleagues have licensed the FAC probe to Sofie Biosciences, which is owned in part by Witte and other UCLA faculty members.