New PET center will aid drug development

Although molecular medicine has made striking advances in recent years, for many diseases physicians are still stumbling in the dark, able to glean clues to a therapy’s effectiveness only by studying changes in symptoms. In many cases, patients may continue to deteriorate while their doctors seek the best treatment. Researchers at Yale’s new Positron Emission Tomography (PET) Center hope to bring light into this darkness and speed the development of new medications by developing novel imaging tools that reveal otherwise hidden molecular abnormalities.

The development of the center was made possible, in part, by Pfizer, the pharmaceutical company, which contributed $5 million to help establish it and provides $2 million annually to support PET imaging studies of mutual research interest to Pfizer and Yale.

The center’s faculty also hopes to build additional alliances with other companies, but the majority of the research conducted at the center is anticipated to be supported by federal research grants.

At a January 18 ceremony marking the official opening of the new 22,000-square-foot facility, George Mills, M.D., director of the Division of Medical Imaging and Radiopharmaceutical Drug Products at the Food and Drug Administration’s Center for Drug Evaluation and Research, said that PET is “the essential foundation” of the agency’s efforts to streamline the development of new medicines.

Also in attendance were Pfizer CEO Jeffrey B. Kindler, J.D., Yale President Richard C. Levin and senior leaders from Pfizer and Yale who played key roles in conceiving the center, including Diane K. Jorkasky, M.D., Pfizer’s vice president of worldwide research operations, Dean Robert J. Alpern, M.D., James A. Brink, M.D., professor and chair of diagnostic radiology, and psychiatry Chair Benjamin S. Bunney, M.D.

In PET, minute amounts of radioactive material known as tracers are chemically attached to drug molecules or other biologically active substances, such as glucose. When these chemically tagged compounds are injected into a patient’s body they bind to specific organ sites, which can be detected and converted into images by the PET scanner (see “A Window into the Body,”). Researchers and clinicians use this information to study changes in organ function as a result of disease or in response to treatment and to determine how much of a drug compound has successfully reached its desired target. PET enables researchers to study the safety and efficacy of different drug doses and to identify biological markers of disease that can aid in diagnosis.

The heart of the new center is a cyclotron encased in a lead radiation shield filled with water; the shield weighs over 100,000 pounds. Within a concrete vault the cyclotron accelerates atomic particles to produce short-lived radioactive isotopes. In an adjacent room, radiochemists collect the isotopes and attach them to appropriate molecules, and the labeled compounds are immediately injected into patients. Then patients lie within the PET scanner, a machine much like a CT scanner that is able to image the accumulation of labeled compounds in specific regions in the body. Yale’s new center boasts one of only 18 PET scanners in the world that can image the human brain at a resolution of 2.5 millimeters.

“The work we do here will build the knowledge we need to develop diagnostic imaging agents coupled to personalized therapy,” says J. James Frost, M.D., Ph.D., M.B.A., professor of diagnostic radiology and psychiatry, chief of nuclear medicine at Yale-New Haven Hospital and director of the new center, located at 801 Howard Avenue in New Haven. Joining Frost as co-directors are lead physicist Richard E. Carson, Ph.D., professor of diagnostic radiology and biomedical engineering and lead radiochemist Yu-Shin Ding, Ph.D., professor of diagnostic radiology. Completing the senior faculty team is Henry Huang, Ph.D., a radiochemist and associate professor of diagnostic radiology.

Pfizer has already used the School of Medicine’s new PET facilities to study a small group of patients to determine how much of a new drug for depression would be required to reach its target in the brain in adequate amounts, and how much would generate unacceptable side effects, according to Jorkasky.

Researchers are usually required to give dosages that escalate over a period of several months to large numbers of patients in order to establish the safest and most effective dose of a drug. “If we are able to avoid the need to do large-scale clinical studies like that, we’ll be saving tons of money and time, and, most important, we won’t expose patients needlessly to a drug that may not have any benefit,” says Jorkasky. Frost says that the center will serve as a core facility for the entire medical school in that some biomarkers discovered in the course of research projects with Pfizer or other companies will be available for faculty research projects.

Along with cardiology and oncology, the center’s major areas of focus are Alzheimer’s disease, schizophrenia, depression, obesity, post-traumatic stress disorder and other conditions that are difficult to diagnose and treat. Frost hopes that the center’s research will help to identify biomarkers for subtypes of these diseases, which can help determine the best treatment for specific individuals. “Ultimately this will benefit our patients,” Frost says. “That’s the key.”

The FDA’s Mills was enthusiastic in his praise for the new center, which he said is equipped with “one of the most intensely high resolution scanners that’s out there.” In particular, Mills lauded the alliance between Yale and Pfizer and the strong links between preclinical and clinical research, animal and human studies, and PET imaging and drug development.

“I’ve seen the critical pathway, and it’s here,” Mills told attendees. “You’ve got it.”