April 30, 2008 — A University of Virginia researcher has received a three-year grant from The Hartwell Foundation to further his research on an innovative method to treat pediatric brain tumors.

School of Medicine biomedical engineer Richard J. Price will receive $100,000 annually for three years for "Targeted Delivery of Chemotherapeutic Controlled-Release Nanoparticles to Common Pediatric Brain Tumors Using Contrast Agent Microbubbles and Ultrasound." Price is the first U.Va. scientist to receive a Hartwell Individual Biomedical Research Award.

Technical advancements in the past decade have made it possible to extend the basic principles of non-invasive, high-intensity, focused ultrasound for destroying organ-confined tumors. However, ultrasound beam aberrations and localized non-specific heating created by the skull are impediments to brain tumor treatment, which could be especially profound in developing children.

By contrast, Price aims to use much lower power levels by deploying "ultrasound-activated" delivery agents comprised of chemotherapeutic drug-bearing nanoparticles adhering to gaseous microbubbles (the size of red blood cells). After injection into the bloodstream and traveling to the site of the tumor, the microbubbles will receive pulsed, focused low-intensity ultrasound treatment that will not heat the skull but will cause the microbubbles to release their contents and thereby initiate destruction of the tumor.

"By activating the nanoparticles with ultrasound, we can hopefully get a more targeted and more sustained release of the chemotherapy drugs. This will potentially provide for fewer treatments with the same efficacy," Price said.

"It is an honor for The Hartwell Foundation to provide financial support to this outstanding researcher," said foundation president Frederick Dombrose. "The competition for awards this year was remarkable, making the final selection very difficult. Participating institutions nominated exceptional individuals, each of whom proposed innovative and cutting-edge science with high relevance in terms of potential benefit to children."

Pediatric tumors respond well to radiation therapy, which is the conventional option according to Price. However, in very young children (less than 4 years old), the side effects of radiation are particularly debilitating (i.e. permanent cognitive deficits, learning disabilities, psychological disorders) because the brain is still actively growing.

"Therefore, the clinician is faced with a difficult Catch 22 – wait until the child is older and risk that the tumor can't be controlled, or treat at an early age knowing that there will be permanent damage," Price said. "Because our treatment approach obviates the need for radiation, these side-effects from radiation are not a concern. Children, who are most sensitive to these side-effects, stand to benefit the most."

Price is an internationally recognized authority on the behavior of small blood vessels and their interaction with drugs and ultrasound-targeted therapeutics. He is a pioneer in the area of microbubble interactions with capillaries.

"This new project will allow him to harness that prior expertise with a new concept for brain tumor therapy that could revolutionize our ability to help patients with this disease. It is a terrific example of how biomedical engineering can help bridge the gap between complex diseases and the new technologies needed to treat them," said Thomas C. Skalak, chairman of the Department of Biomedical Engineering at the School of Medicine.

Last year, The Hartwell Foundation selected U.Va. as a Hartwell 2007 Top Ten Center of Biomedical Research, offering the University the opportunity to nominate four candidates for consideration as Hartwell Investigators. By participating in the Hartwell process, U.Va. qualified to receive one Hartwell Fellowship to fund a postdoctoral researcher designated by the University. Cynthia Grimsley-Myers of the Department of Cell Biology received the award, which will enable her to pursue further specialized research training on defects in inner-ear development, a leading cause of childhood deafness.

Based in Memphis, Tenn., the primary mission of the Hartwell Foundation is to grant awards to individuals for innovative and cutting-edge biomedical applied research that potentially benefit children. The general aim is to provide funds for early-stage research projects that have not yet qualified for funding from traditional sources. In making Individual Biomedical Research Awards, The Hartwell Foundation takes into account the nature of the proposed innovation, the extent to which translational approaches will promote rapid clinical application of the research results, the supportive role of collaboration, and the institutional commitment to provide encouragement and technical support.

"We are very grateful for The Hartwell Foundation's generous support of our research approaches in children's health," said Dr. Sharon L. Hostler, interim vice president and dean of the School of Medicine. "Dr. Price's work on pediatric brain tumors may bring new hope and treatment options to children and families facing cancer."

More information about The Hartwell Foundation is available on its Web site, www.thehartwellfoundation.org.