Real-Time Visualization of Tumor Metabolism Possible with New Prostate Cancer Imaging Technology

Research collaboration has produced the first results in human trials of a new technology that has the potential to evaluate quickly the presence and aggressiveness of prostate tumors in real time, by imaging the tumor's metabolism. This is the first time researchers have employed this technology to perform real-time metabolic imaging in a human patient and represents a groundbreaking approach to assessing the precise outlines of a tumor, its response to treatment, and how rapidly it is growing.

Data on the first four patients were presented on December 2, 2010, at the Radiology Society of North America's (RSNA) weeklong annual conference held in Chicago, IL, USA. The initial results, from a collaboration of researchers from the University of California, San Francisco (UCSF; USA) and GE Healthcare (Chalfont St. Giles, UK), confirm extensive preclinical research that has tied the speed at which tumors metabolize nutrients to the aggressiveness of their growth. The new imaging technique also has been used to show early biochemical changes in animal tumors in real time as they respond to medication therapy, long before a physical change occurs.

Up to now, the technology has produced the same response in human patients' tumors as it did in laboratory studies, even at the lowest dose, according to Sarah Nelson, PhD, a professor of radiology and biomedical imaging and a member of the California Institute for Quantitative Biosciences (QB3) at UCSF. "This is a key milestone that could dramatically change clinical treatment for prostate cancer and many other tumors,” Dr. Nelson said. "We had shown this worked in animal models and tissues samples. Now, in men, we are seeing exactly the type of results we had hoped for.”

The method uses compounds involved in normal tissue function--in this case, pyruvate, which is a naturally occurring by-product of glucose, and lactate, also known as lactic acid--and uses newly developed equipment to increase the visibility of those compounds by a factor of 50,000 in a magnetic resonance imaging (MRI) scanner.

That process requires pyruvate to be prepared in a strong magnetic field at a temperature of -272 ^oC, then rapidly warmed to body temperature and transferred to the patient in an MRI scanner before the polarization decays back to its native state. The result is a highly defined and clear image of the tumor's outline, as well as a graph of the amount of pyruvate in the tumor and the rate at which the tumor converts the pyruvate into lactate.

The procedure must take place within minutes, which meant integrating a clean room into the scanning facility. The first trial involves men with prostate cancer involved in the "watchful waiting” phase of treatment, according to Dr. Nelson. Future studies will directly compare these data with the findings from surgically removed tumors and will look at how specific therapies change tumor metabolism. UCSF also will be studying the process for use in brain tumor patients.

For an oncologist, that means immediate feedback on whether a patient's therapy is working, either during standard treatment or in a clinical trial. "If we can see whether a therapy is effective in real time, we may be able to make early changes in that treatment that could have a very real impact on a patient's outcome and quality of life,” said Andrea Harzstark, MD, an oncologist with the UCSF Helen Diller Family Comprehensive Cancer Center who is leading the clinical aspects of the current study.

The disease ranges widely in its rate of growth and aggressiveness, according to John Kurhanewicz, PhD, a UCSF expert in prostate cancer imaging. As a result, there is great debate over the ideal strategy for treating the disease, he reported, leaving patients with a difficult and potentially life-changing decision over how aggressively to respond to the disease.

"This test could give both physicians and patients the information they need to make that decision,” said Dr. Kurhanewicz, whose work with Dan Vigneron, PhD, and their colleagues from the UCSF department of radiology and biomedical imaging first linked a prostate tumor's production of lactate to tumor aggressiveness. Other researchers also have linked that lactate production to tumor aggressiveness and response to therapy in other cancers.

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