Public Release: 

Novel Imaging Agent Developed By Penn Researchers Provides Insight Into Brain's Message Delivery System

University of Pennsylvania School of Medicine

(Philadelphia, PA) -- How the brain works and why it malfunctions remains a mystery that drives scientists and physicians to seek answers. A scientific triumph in this crusade occurred when an advanced brain imaging agent, called Trodat, was developed at the University of Pennsylvania Medical Center. This imaging agent could be a key to the understanding of brain disorders like Parkinson's and Alzheimer's diseases.

To acknowledge this milestone, the European Journal of Nuclear Medicine (EJNM) will present one of its highest honors -- the Award for Best Science Paper in 1997-- to Hank F. Kung, PhD, professor and Chief of Radiopharmaceutical Research at the University of Pennsylvania Medical Center. The award will be given at the Joint Congress of the European Association of Nuclear Medicine and the World Federation of Nuclear Medicine and Biology held in Berlin, Germany, August 30 - September 4, 1998.

This award recognizes the breakthroughs of Dr. Kung and a multi-disciplinary team of researchers at Penn, including chemists, radiologists, psychiatrists, and pharmacologists. The paper, entitled, "[99mTc] Trodat-1: a Novel Technetium-99m Complex as a Dopamine Transporter Imaging Agent*," describes the development and study of a groundbreaking new brain tracer, or imaging agent, used to evaluate brain function in normal and disease states. Commonly known as Trodat, this new tracer is a derivative of tropane -- a minimally-radioactive chemical that follows the flow of a chemical messenger in the brain called dopamine -- and can be used as a diagnostic tool for imaging dopamine transporters.

"The dopamine system in the brain contains receptors that control basic functions like ovement, memory, and emotion," explains Dr. Kung. "Trodat can be used to determine whether the dopamine transporter is working correctly, or, if it is unbalanced which leads to neurological and psychological illnesses that are linked to dopamine changes."

Dopamine transporters are protein complexes ocated at the presynaptic (forepart) of dopamine nerve terminals which function to deliver messages to receptors in the brain. A significant reduction in the density of these transporters has been found in postmortem examinations of the brains of Parkinson's and Alzheimer's patients. Thus, measurement of the dopamine transporter with Trodat could be a useful indicator of dopamine neural loss. With advanced radiologic imaging technology, such as single positron emission tomography (SPET) -- which works by emitting photons or light -- Trodat can be a valuable tool for live diagnosis and treatment of illnesses associated with dopamine transporters. Such illnesses include Parkinson's and Alzheimer's, as well as schizophrenia and ALS (Lou Gehrig's disease).

In this study, Trodat was intravenously injected into rats. Trodat displayed specific brain uptake in the rats' striatal region of the brain where dopamine neurons are concentrated. The study's findings strongly support the conclusions that Trodat binds selectively to dopamine transporters in the brain and that it is potentially useful in the assessment of neuron loss. Compared to other imaging agents, Trodat is favorable because it involves very little radioactivity, has a six-hour physical half-life, and is inexpensive. This tracer, coupled with SPET imaging, can provide diagnostic information not attainable by other imaging techniques, including early indications of diseases associated with dopamine changes. Research continues into more advanced stages with goals to ultimately translate findings into clinical applications for patients. Recently, research has progressed to human studies using Trodat.

The University of Pennsylvania Health System is dedicated to developing leaders in science and medicine through education, research, and quality patient care. Penn was selected as the winner of the 1998 National Quality Health Care Award, one of the industry's most prestigious honors. In addition, the Hospital of the University of Pennsylvania (HUP) ranked among the nation's best in many key specialties by US News & World Report; and the School of Medicine currently ranks third among academic medical centers in the U.S. for sponsored research and training awards from the National Institutes of Health. More information about the University of Pennsylvania Health System is available through Penn's website at http://www.med.upenn.edu.

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Editor's Notes: Dr. Kung is available for interviews and can be reached directly at (215) 662-3096. Call Diane Giaccone in Public Affairs at (215) 662-2098 to reach Dr. Kung while he is attending the joint nuclear medicine meeting in Berlin, August 30 - September 4, 1998.

*The original paper appeared in the April 4, 1997, issue of the European Journal of Nuclear Medicine, Volume 24. Research funding was provided by grants awarded by the National Institutes of Health.

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