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Chemistry building at Brookhaven Lab named Historic Chemical Landmark
Oct 19, 2012 - 4:00:00 AM

UPTON, NY -- The New York Section of the American Chemical Society (ACS) has designated the Chemistry Building at the U.S. Department of Energy's Brookhaven National Laboratory as an Historic Chemical Landmark.* This designation honors the synthesis of 18^FDG, a radiotracer that has had a revolutionary and global impact on cancer diagnosis and management and brain research. Originally synthesized at Brookhaven Lab in 1976 for positron emission tomography (PET) scanning, 18^FDG is now the world's most widely used radiotracer for cancer diagnosis, with more than 1.5 million 18^FDG PET scans performed annually.

This recognition is a great honor for Brookhaven Lab as a whole, and particularly for the chemists who performed this seminal work, including Joanna S. Fowler and her colleagues, who continue to explore innovative applications for radiotracer and imaging technologies, said Brookhaven Laboratory Director Samuel Aronson. The development of 18^FDG is also a testament to one of the key strengths of the national laboratories, which bring together scientists from a range of disciplines in an environment that fosters collaborative approaches to address some of our nation's toughest challenges.

As Fowler recalls, We were fortunate to have so much expertise in organic synthesis and radiochemistry with short lived isotopes like fluorine-18 'in house' in Brookhaven's Chemistry Department-specifically Al Wolf, Tatsuo Ido, Vito Casella, and Chung Nan Wan, who worked directly on the 18^FDG problem, she said. But we also benefited from the expertise of other scientists at the Lab, including other chemists, physicists, and engineers who worked on early detector technology and advanced our understanding of radioactive elements.

External collaboration was also essential to the 18^FDG success story. The original idea of radioactively tagging 2-deoxyglucose (2-DG), a molecule related to glucose, to create a radiotracer that could be used to image metabolic activity in the brain came from Louis Sokoloff at the National Institutes of Health (NIH) and Martin Reivich at the University of Pennsylvania. Glucose is the body's main source of energy. 2-DG goes wherever glucose is needed in the body. But instead of being completely metabolized to produce energy, it gets trapped at the site of metabolism. So a radioactive tag would give scientists a way to track this glucose stand-in's location and concentration in the body. Sokoloff and Reivich turned to the chemistry experts at Brookhaven to figure out which isotope to use, where to place it on the 2-DG molecule, and to develop the tricky synthesis technique.

The Brookhaven chemistry group had recently pioneered the development of 18^F-labeled elemental fluorine gas. They suggested that this gas could be used to label 2-DG, with the 18^F atom substituting for a hydrogen atom at position 2 on the molecule. They predicted that this configuration would allow the tracer to mimic the behavior of 2-DG.

At first this seemed like an insurmountable challenge, recalled Fowler. Not only did we need to develop a very rapid synthesis from the very reactive fluorine gas, but we had to make enough to make up for radioactive decay for the trip from Brookhaven to Philadelphia, where the imaging would be done. Fortunately, by working at low temperatures and with dilute samples, we were able to 'tame' the reactivity, she said.

After the Brookhaven team synthesized the first samples, NIH collaborators confirmed that the fluorine atom did not otherwise alter the parent molecule. Samples of 18^FDG were quickly flown to Pennsylvania, where Reivich and his colleagues first used the tracer to map brain glucose metabolism in humans using the Mark IV scanner developed by David Kuhl. Later, Prantika Som of the Medical Department at Brookhaven published one of the very early papers outlining the use of 18^FDG in cancer diagnosis, which has proven to be its most clinically useful application.

We couldn't have done this work, or continue what we do today, without the combined expertise of chemists, biologists, physicists, and medical doctors and the long term investment in chemistry and physics by the Department of Energy and its predecessor agencies, Fowler said.

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