New metabolic PET tracer finds deep brain tumors, helps monitor treatment

Stanford University researchers have developed a molecular tracer capable of locating and subsequently following a cancer-elevated protein in hard-to-find brain tumors.

The tracer did its job identifying and isolating the protein in mice, according to a paper published Oct. 21 in Science Translational Medicine.

Stanford investigators say they expect the tracer to win FDA approval for human trials in about a year.

They based their approach on the tendency of rapidly dividing cancer cells to express higher-than-normal levels of the protein pyruvate kinase M2 (PKM2).

The new tracer, called [11C]DASA-23, works especially well in the brain because normal brain cells have very low levels of PKM2 “dimers,” which are complexes of two PKM2 molecules.

According to Stanford Medicine’s news office, the researchers already knew that cancer cells tend to have higher levels of PKM2 dimers.

Combining this insight with the knowledge that members of the molecule family called DASA bind to the dimer, they labeled one family member, DASA-23, with a radioactive carbon molecule.

Augmented by the new tracer, PET scans allowed the team to observe the labeled molecule as it sought out and bound to human glioblastoma cells implanted in the brains of the mice.

The brain cancer cells stood out clearly against a background of normal, noncancerous cells.

Sanjiv Sam Gambhir, MD, PhD, a radiology professor at Stanford and director of its molecular imaging program, told the news office this is the first time researchers have been able to “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,” he explains. “So we could know very quickly, possibly within a few days, whether the therapeutic approach is working. If it’s not effective, we won’t have to waste a month or more waiting to see if the tumor itself is shrinking.”

Gambhir adds that the new tracer could be used in cancers other than those in the brain, “or to even learn more about how normal tissues adjust their metabolism during development or in response to varied environmental conditions.”