About 10 percent of patients with colorectal cancer express a mutated form of the signaling molecule BRAF, which may be targeted for treatment by selective BRAF inhibitors. PET (positron emission tomography) imaging using a standard glucose probe is not able to predict response to BRAF inhibitors.
In addition to becoming dependent on glucose, cancer cells exhibit increased dependency on the amino acid glutamine. H. Charles Manning, Ph.D., and colleagues explored the use of a glutamine PET probe to predict response to mutant BRAF-targeted therapy in preclinical mouse models of colon cancer. They found that glutamine PET imaging predicted response to BRAF inhibition in tumors expressing mutant BRAF, but not in tumors expressing wild-type BRAF.
The findings, reported in the June issue of Molecular Imaging and Biology, demonstrate the utility of non-invasive PET imaging of glutamine uptake to predict response to BRAF-targeted therapy in colon cancer and could improve patient selection in colon cancer trials using BRAF-targeted therapies.
This research was supported by grants from the National Institutes of Health (CA140628, CA095103, DK058404, CA068485), the Kleberg Foundation, and the Vanderbilt Center for Molecular Probes.