Sugar compound could enhance prostate imaging

A natural form of sugar could offer a new, noninvasive way to precisely image prostate and other tumors and potentially see whether cancer medication is effective, by means of a new imaging technology.

The technology, developed at the University of California, San Francisco in collaboration with GE Healthcare, uses a compound called pyruvate, which is created when glucose breaks down in the body and which normally supplies energy to cells. In cancer, however, pyruvate is more frequently converted to a different compound, lactate.

Previous animal studies showed that scientists could track the levels of pyruvate as it is converted to lactate via magnetic resonance imaging (MRI), by using a technology called hyperpolarization and injecting the hyperpolarized pyruvate into the body. The amount of lactate produced and rate of conversion enabled researchers to precisely detect the limits of a mouse’s tumor, identify which cancers were most aggressive, and track early biochemical changes as tumors responded to medication, long before physical changes occurred.

Now, a 31-patient study performed by scientists at UCSF and collaborators at GE Healthcare and published online in Science Translational Medicine (Aug. 14, 2013) has shown that the technology is safe in humans and effectively detects tumors in patients with prostate cancer.

While this first-in-human study was designed to identify a safe dosage and verify effectiveness, it lays the groundwork for using the technology to diagnose a variety of cancers and track treatment noninvasively without conducting repeated biopsies, researchers say.

“We now have a safe dose for patients-that was our primary goal,” said lead author Sarah J. Nelson, PhD, of UCSF.

“In animal models, the amount of lactate over pyruvate is directly related to the aggressiveness of the cancer. We also have a lot of data that show it’s reduced in cancers after treatment. This is a very ubiquitous molecule that will be important in tailoring treatments to specific individuals,” Dr. Nelson said.

The real-time imaging could provide immediate feedback on whether a patient should continue active surveillance of the tumor or pursue treatment and also whether a therapy is working, either during standard treatment or in a clinical trial.

For the study, which started in December 2010, the authors labeled pyruvate with carbon-13 and injected this “hyperpolarized pyruvate” imaging agent into 31 prostate cancer patients at UCSF. The team then used an MRI to follow pyruvate and its conversion to lactate in the prostate.

As in previous studies in mice, the higher, more intense signals indicated a more rapid conversion to lactate, possibly a sign of more aggressive cancer. In contrast, there was very limited conversion detected in normal prostate.

The study deliberately focused on patients with low-grade tumors who had not yet received treatment to identify the safe and appropriate dosage of pyruvate needed. Future studies will use the technology to assess the effectiveness of a patient’s cancer therapy in shrinking their tumor-knowledge that will enable physicians to assess the dosage of chemotherapy needed on an individual basis.

The polarizer and costs of the carbon-13 patient studies were supported with funding from GE Healthcare.

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