Metabolic Imaging Points Out Prostate Cancers

The first clinical trial of imaging tumor metabolism using hyperpolarized MRI shows that the technique is safe in humans and can highlight differences in how normal and cancerous prostate tissues metabolize sugars (Sci Transl Med 2013:198,198ra108). If confirmed in further studies, the approach may provide a noninvasive way to analyze the aggressiveness of prostate tumors and monitor response to therapy.

“We know that metabolism is a good way to assess the aggressiveness of a tumor,” says Sarah Nelson, PhD, a professor of radiology at the University of California, San Francisco (UCSF), and lead author on the paper. Tumor tissue has a different metabolism from healthy tissue and tends to convert the sugar pyruvate into lactate rather than into other metabolites, she explains. This conversion is more pronounced in more-aggressive tumors.

The effect is invisible in conventional imaging scans but can be observed by MRI with a special contrast agent treated to generate a hyperpolarized spin state in a carbon-13 nucleus in pyruvate. This results in a 10,000-fold enhancement in image contrast relative to conventional MRI.

While hyperpolarized pyruvate has been used to image abnormal metabolism in tumors in animals, it hasn't been safe to use in humans. The agent can be created only at temperatures nearing absolute zero—much too cold to inject into the human body—and must be warmed and injected quickly because its half-life is only about 60 seconds.

Nelson's group at UCSF developed a way to rapidly filter and warm the hyperpolarized pyruvate so that it can be injected in an arm within 66 seconds, with observable uptake following within 20 seconds. The group also designed special pulse sequences for the MRI scanner, and coils to create the pulses.

The researchers and their colleagues tested the safety of the agent in a clinical trial of 31 men with biopsy-proven early-stage prostate cancer. They found no dose-limiting toxicity. Areas known to be cancerous had higher levels of lactate relative to pyruvate than normal tissues, and in some cases cancer was identified in regions where it had not been seen by other imaging methods.

With the current widespread use of prostate-specific antigen blood tests, “a lot of men are getting a diagnosis of cancer, and we don't know if it's going to be aggressive or benign,” says Nelson. She hopes that metabolic imaging will help doctors make better treatment decisions and monitor therapeutic responses.

Robert Gillies, PhD, vice-chair of radiology and director of imaging research at the Moffitt Cancer Center in Tampa, FL, is excited to see hyperpolarized MRI in human studies. “We can follow not only where these substrates go but what they get turned into, and measure the flux of metabolic reactions in real time,” he says. Gillies adds that the technology allows more extended tracing of metabolites over time than does positron emission tomography (a common tool for imaging tumors) and is likely to be less expensive.

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