Tracing Agent, Ultrasound Combo Helps Test Cancer Therapy's

[RandyW]

An inexpensive tracing agent used in combination with ultrasound can pinpoint how effectively drugs targeting pancreatic cancer work, researchers at UT Southwestern Medical Center have demonstrated for the first time.

The study, involving human pancreatic tumor cells implanted in mice, opens a new avenue for real-time imaging of a patient's response to cancer therapies. It appears in the Jan. 1 issue of the journal Clinical Cancer Research.

"In general, it has been difficult to assess whether anti-angiogenic drugs are having an impact on tumors in human patients," said Dr. Brekken. "The sooner we can measure the effectiveness of the treatment, the earlier we can intervene to change anti-cancer agents if a particular drug has no effect. This could be a lifesaving approach in patients with rapidly fatal disease."

To find the answer, the UT Southwestern team resorted to an inexpensive and commonly used contrast, or tracing agent, called microbubbles. Each tiny bubble measures about one to two microns in diameter - about a hundredth the width of a human hair - and consists of albumin, sugar and an inert gas. Microbubbles are used routinely in echocardiography, for example, allowing cardiologists to see how efficiently and how much blood the heart pumps.

UT Southwestern researchers linked the microbubbles to a targeting agent that delivered the imaging agent to proteins or protein complexes on the surface of tumor blood vessels. They found that the ultrasound signal from the microbubbles decreased in mice that received therapy. The harmless microbubbles remained in the bloodstream and allowed researchers to use ultrasound to get a crisp picture of what was occurring on blood vessels inside the tumor, Dr. Brekken said.

In one of the studies reported, the researchers observed that blocking VEGF activity achieved a 40-percent reduction in mean tumor size after four treatments over a two-week period, a significant controlling of tumor growth, Dr. Brekken said. Importantly, the reduction in tumor size was predicted by the decrease in signal observed non-invasively with the targeted microbubbles.

"Ultrasound is a safe technology and most physicians have an ultrasound machine in their office," Dr. Brekken said. "In addition, this monitoring technology would neither require radiation nor the injection of toxic substances for imaging purposes.

We are the first group to show that this technique can be used to monitor the effectiveness of an anti-cancer agent," he said.

The monitoring method developed by Dr. Brekken and his colleagues would need to obtain approval from the U.S. Food and Drug Administration before it could be used in humans. Microbubbles will have to be engineered for human patients and these microbubbles will need to be linked to anti-cancer agents using chemicals acceptable to the FDA for use in humans.

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The research was supported by a grant from Peregrine Pharmaceuticals Inc, a biopharmaceutical company that has an exclusive license from the University of Texas System for the anti-VEGF agent that Dr. Brekken and other UT Southwestern researchers developed and are testing in several preclinical studies. Dr. Brekken also is a consultant to and has equity interest in the company.

Other UT Southwestern researchers contributing to the study included Juliet Carbon, a senior research associate at the Hamon Center; lead author Dr. Grzegorz "Greg" Korpanty, formerly a researcher at the Hamon Center and now a resident in internal medicine at Mater Misericordiae University Hospital in Dublin, Ireland; and Dr. Jason Fleming, former associate professor of surgery at UT Southwestern and now a surgical oncologist at the University of Texas M.D. Anderson Cancer Center. A researcher from Baylor University Medical Center in Dallas also participated.

About UT Southwestern Medical Center

UT Southwestern Medical Center, one of the premier medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. Its more than 1,400 full-time faculty members - including four active Nobel Prize winners, more than any other medical school in the world - are responsible for groundbreaking medical advances and are committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 89,000 hospitalized patients and oversee 2.1 million outpatient visits a year.