New Metabolic PET Tracer Can Help Find Brain Tumors and Improve Cancer Therapy Outcomes

The Stanford team used this property of cancer cells, and developed a molecular tracer to track the activity of a key regulatory protein called pyruvate kinase M2 (PKM2) that helps control the metabolism of tumor cells. The tracer enabled the researchers to track the precise location of cancer cells in the brain. According to the researchers, the tracer could also help provide feedback about how a tumor is responding to therapy.

Pyruvate kinase is a key regulator in the cellular process of metabolizing energy sources such as glucose. Cells can either convert energy into the co-enzyme Adenosine Triphosphate (ATP), or use the energy to generate amino acids and other cellular building blocks. When pyruvate kinase exists as a dimer, a complex of two pyruvate kinase molecules, it favors the accumulation of amino acids. When the protein exists as four molecules bound together the cell generates more ATP. Cancer cells have higher levels of the dimer, and DASA molecules bind to the dimer. The researchers labeled DASA-23 molecules with a radioactive carbon molecule, and used PET scans observed how the DASA-23 molecules found, and bound to human glioblastoma cells, implanted in the brains of mice. The technique was able to highlight the brain cancer cells clearly among the normal, non-cancerous cells. The researchers expect the new [11C]DASA-23 tracer to be approved by the US Food and Drug Administration (FDA) for use in humans by Fall 2016.

Sanjiv Sam Gambhir, MD, PhD, director Molecular Imaging at Stanford, senior author of the research, said, “Tumor cells do all kinds of things to survive and prosper in the body. One of the key things they modify is a master switch that controls cell metabolism and allows the cell to make more of the building blocks necessary for cell division. But until now we’ve had no way to assess the presence or activity levels of the PKM2 protein involved in that switch. This is the first time we can noninvasively interrogate the biochemistry of a tumor with respect to this master switch PKM2. If we treat a tumor with a drug, we now see whether the cancer cells’ metabolic properties are changing. So we could know very quickly, possibly within a few days, whether the therapeutic approach is working. This new molecule, or tracer, works particularly well in the brain because normal brain cells have very low levels of PKM2 dimers. It’s possible, though, that this tracer could also be used in cancers in other tissues like the prostate, or to even learn more about how normal tissues adjust their metabolism during development or in response to varied environmental conditions.”

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Stanford School of Medicine