Imaging Method Targets Cancerous Tumors

It is possible that one day their detection method could be used as a universal procedure, similar to mammography or colonoscopies. Their noninvasive imaging test could target a problem before the patient ever feels ill.

The researchers, University of Rhode Island (URI; Kingston, RI, USA) associate professors, biophysicists Drs. Yana Reshetnyak and Oleg Andreev, have attracted more than US$6 million in grants in four years. In addition, a number of healthcare and pharmaceutical companies have expressed interest in their work.

The key lies in the acidity level of cells. While normal cells maintain a pH of 7.4 with little variation, cancer cells expend a great deal of energy as they rapidly proliferate, driving protons outside and creating an extracellular pH level of 5.5-6.5 (the lower the number, the higher the acidity). While scientists have known about tumor acidity for quite a while, they had not devised a way to target it. Dr. Donald Engelman, from the molecular biophysics and biochemistry lab at Yale University (New Haven, CT, USA; www.yale.edu), discovered the peptide that targets acidity, but had not employed it until Dr. Reshetnyak joined his lab as a postdoctoral student in 2003. She and Dr. Andreev, then a senior scientist at an anticancer drug delivery company, suggested an investigation into the peptide's potential as cancer targeting agents.

In 2004, Drs. Reshetnyak and Andreev joined the physics department at URI and established a biologic and medical physics laboratory. The couple continued their collaboration with Dr. Engleman and their investigation of the characteristics of the peptide, now called the pHLIP (pH [Low] insertion) peptide. After making some modifications to it, they demonstrated that pHLIP could find a tumor in a mouse and deliver imaging or therapeutic agents specifically to cancer cells. The Yale/URI targeting system has a patent pending in the United States and Europe.

The researchers suggest their discovery method could be used to monitor other disease development and treatment. It also could play an important role in the study of arthritis, inflammation, infection, infraction, and stroke since those conditions also generate high acidity. In addition to targeting cancerous tumors, the researchers discovered a novel delivery agent, a molecular nanosyringe, which can deliver and inject diagnostic or therapeutic agents specifically to cancer cells. "Since we know the mechanism of delivery and translocation, we believe that we are able to tune the nanosyringe properties and engineer a novel class of therapeutic and diagnostic agents,” noted Dr. Reshetnyak.

In a project with the Cancer Center at Rhode Island Hospital (Providence, USA), the URI researchers have successfully shown that the peptide can deliver nanogold particles into the cancerous tumor. Once in place, the tiny gold particles can absorb more radiation, providing a more deadly dose to the tumor, but not to surrounding health cells.

"Drs. Reshetnyak and Andreev research offers a potential for a new and more effective approach to the treatment of cancer with radiation, making it highly intriguing and important,” said Dr. Edward S. Sternick, medical physicist-in-chief, department of radiation oncology, Rhode Island Hospital and professor and vice chair radiation oncology at the Warren Alpert Medical School of Brown University (Providence, RI, USA). "About 1.6 million new cancer patients are diagnosed annually in the U.S.,” stated Dr. Sternick noting that the number is expected to grow significantly, reaching two million cases per year in the next 10 years, a direct reflection of our aging population. Approximately 50% of these cancer patients will receive radiation therapy during the course of their disease.”

The URI researchers are collaborating on a $1.5 million U.S. National Institutes of Heath/National Cancer Institute (Bethesda, MD, USA) grant. Dr. Jason S. Lewis, chief of radiochemistry services at Memorial Sloan-Kettering Cancer Center (New York, NY, USA), commented, "Their research is innovative and exciting. It is also timely; the understanding of the tumor microenvironment, and in particular, the pH of a tumor is believed to be important in the metastatic spread of cancer. The technology that the couple has developed could predict noninvasively the metastatic potential of cancer as well as or monitoring the effectiveness of potential therapies. Their technology may allow for patient personalized therapies in the future.”

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