APRIL 2003

PET reporter genes track T cell antitumor response

By: Charles Bankhead

CONTEXT: FDG-PET imaging offers the potential for noninvasive monitoring of immune system function for various clinical applications and diseases, according to findings from ongoing studies at the University of California, Los Angeles.

RESULTS: A study designed to demonstrate proof of principle resulted in PET images that documented specific localization of transferred T-cells, but not native T cells, to antigen-positive tumors in mice. The T cells that demonstrated localization had been removed from the spleens of animals that had successfully rejected experimentally induced tumors. The T cells were marked with a PET reporter gene, and following injection into tumor-bearing mice, localization of the immune T cells to the tumors was detected over time by sequential imaging of the animals with microPET, using an enzyme substrate specific for the reporter (Proc Natl Acad Sci USA 2003;100:1232-1237).

IMAGE: MicroPET F-18-FHBG image uncovers an antigen-positive tumor on the mouse subject's left side and an antigen-negative tumor on the right side. Signal on the left arises from the localization of T cells at the tumor site. (Provided by P. Dubey)

IMPLICATIONS: "In comparison to MRI and CT, PET is far more sensitive in terms of resolution," said Purnima Dubey, Ph.D. "The other methods also do not utilize an enzyme substrate reaction the way we do. We can specifically label a cell population of interest."

PET imaging of the immune system has potentially broad applications in preclinical and clinical settings. It could, for example, be used to evaluate the effects of perturbations to potentiate or block the immune response in animal models, Dubey said. In humans, quantitative PET imaging could be used to evaluate immunotherapy protocols.

Ongoing studies by Dubey and her associates include explorations into the potential of cytokines, antibodies, and other immunomodulatory agents to enhance T-cell activity.