PET tracer identifies which liposarcoma tumors may respond to chemotherapy

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Researchers have identified a group of liposarcoma tumors that can be imaged by positron emission tomography (PET) scans using a tracer substance known as FAC. In addition, these tumors were found to be sensitive to chemotherapy.

Liposarcoma, the most common type of sarcoma, is an often lethal form of cancer that develops in fat cells. High mortality is due in part because the tumors are not consistently visible with PET scans using the common FDG probe and that the tumors frequently do not respond to chemotherapy.

The scientists used a metabolomic strategy that detected nucleoside salvage activity in liposarcoma cells taken from patient samples, cells grown in the laboratory, and cells grown in mouse models. The nucleoside activity was visible using PET with the UCLA-developed FAC probe (FAC PET). The FAC probe measures the activity of the DNA salvage pathway, which is a fundamental cell biochemical pathway that acts as a sort of recycling mechanism for DNA replication and repair.

FAC was created by slightly altering the molecular structure of the standard chemotherapy drug gemcitabine. This study found that liposarcoma cells with high nucleoside salvage activity were sensitive to gemcitabine chemotherapy.

In clinical practice, this strategy may be able to identify which patients with liposarcoma would respond well to gemcitabine therapy at the time of diagnosis. This would save time on other treatments and possibly extend the lives of this subgroup of patients.

“It was a satisfying study because it has translational potential for liposarcoma patients now—and this is a deadly disease,” said Heather Christofk, PhD, of UCLA's Jonsson Comprehensive Cancer Center. “Our metabolomic strategy is also generalizable to treatment strategies for other cancers, and that is something we hope to do.”

Her coinvestigator Fritz Eilber, MD, also of UCLA, said, “This was an outstanding transdisciplinary project between a diverse group of physician scientists and basic scientists that translates molecular oncology from the laboratory to the clinic in a rapid and clinically relevant manner. The findings from this work can be used to directly impact the care of patients with this morbid and lethal malignancy.”

This study was published in Cancer Discovery (2012; doi:10.1158/2159-8290.CD-12-0197).

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