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Chemists Develop Probe To Detect Changes In Imaging Agents Inside Body

University of Cincinnati

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Cincinnati -- Chemists at the University of Cincinnati have found a way to determine what happens to medical imaging agents as they travel through the body and accumulate inside various tissues and organs.

The agents combine a radioactive tracer such as technetium with a ligand or compound that can target the tissue or organ of interest. For example, a common application is a heart imaging agent which can detect blockages in blood flow following a heart attack. This information is important to doctors planning follow- up therapy and rehabilitation.

"Doctors can get very good images this way," said Distinguished Research Professor William Heineman who has studied the fundamental chemistry of several heart, skeletal and brain imaging agents at UC. "You see bright regions where muscle tissue is normal and very dark areas where blood flow is blocked."

Heineman is an analytical chemist who also has a great deal of experience developing sensors which can detect compounds at extremely low concentrations, as low as 3,000 molecules. So, in his recent research, Heineman, chemistry professor Carl Seliskar, and chemistry graduate students decided to try to develop a sensor to see if they could monitor what happens to an imaging agent after it enters the body.

"We just happened to be in a unique position of knowing something about nuclear medicine and also about developing sensors. We're probably the only group in the world with those two skills."

The sensors are tiny carbon fibers, the same graphite fibers used to make lighter tennis rackets and golf clubs, coated with a thin layer of polymer. The package then becomes a probe which can be inserted directly into the heart tissue.

"We can get these fibers as free samples and simply take out a single fiber and make it into a sensor by coating it with the polymer that gives us the selectivity needed to detect the imaging agent in the presence of other compounds in tissue. Then we insert it into the organ of the animal, and make a measurement. That's how we do it."

Doctoral candidate Maria Theresa Lee has the difficult job of producing the probes which are so fragile they have to be encased in a tiny capillary of glass. "You can hardly see the fibers," remarked Lee. "It's very difficult when you're making it. You have to be careful breathing or else it just flies away."

Lee hopes her probes will lead to the development of even better imaging agents, because the probes will show radiologists what happens chemically to the imaging agent as it travels through the bloodstream. Scientists in the department of radiology in UC's College of Medicine are researching that part of the problem.

"Nobody knows exactly what happens to the compound in the body," said Lee. "It's a very harsh and complex environment, and no one knows what happens to it."

Lee presented her results from in vitro testing during the recent Pittsburgh Conference on Analytical Chemistry. She is now testing her probes on live animals in collaboration with radiology professor Anthony McGoron who presented their work at the Society of Nuclear Medicine meeting in Denver, Colorado in June. So far, the probes appear to be working well despite concerns over their stability.

"You have the heart beating and bumping, and you know how fragile the carbon fiber is. We tried it, and we didn't have any problems with it."

Professor Heineman believes the probes could eventually be used to study other medically important compounds such as brain imaging agents and kidney imaging agents, but he realizes a lot of research remains to be done.

"We've just demonstrated that we have the capability to do this, so it's opened up a frontier. We've opened the door, but we haven't taken too many steps yet."

In fact, all of the preliminary research has been done using rhenium complexes instead of technetium to avoid the difficulties of working with radioactive materials. Rhenium is chemically similar to technetium, but does not carry the same radioactive risk.

The research is funded by the U.S. Department of Energy.


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