Radiochemistry Breakthrough Improves Mapping of the Brain

PET Centre Profile: Dr. Alan Wilson

Dr. Alan Wilson of the PET Centre leads a radiochemistry team that produces radiotracers. These radioactive chemical compounds are the foundation of positron emission tomography (PET), an advanced imaging technique that makes a three-dimensional map of the brain. As a radiotracer decays, the energy it creates allows scientists to photograph and study areas of the brain.

“To be safe for use in human studies, the tracers must decay quickly,” says Dr. Wilson. “ Because of this, we have to make fresh tracers for each experiment, and do it all within in an hour to ensure the compound has enough radioactivity to be effective. ”

Dr. Wilson is continually working on creating new radiotracers, which will provide more information on addictions and on illnesses such as Parkinson’s disease and schizophrenia. In the June 2005 issue of the Journal of Medicinal Chemistry, Dr. Wilson and other CAMH colleagues* reported on their groundbreaking work in developing the first dopamine D2 agonist radiotracer used in humans.

Neurotransmitters (chemical messengers), such as dopamine, work by binding to receptors (specialized brain cells that receive the chemical message). For example, dopamine binds to a receptor called D2. Dopamine is an agonist transmitter: rather than blocking the receptor, it causes the receptor to do what it is designed to do. Dr. Wilson’s new agonist radiotracer will allow researchers to better understand how dopamine and the D2 receptor work.

Scientists around the world have tried to make agonist radiotracers for the past 15 years. “People kept saying it wouldn’t work,” says Dr. Wilson. But CAMH scientists made it happen.

Using schizophrenia as an example highlights the significance of this achievement. Most receptors, including D2, exist in either a high or low affinity state. This means that either a large or a small amount of dopamine binds to the receptor. One theory in schizophrenia research is that people with this illness have more high affinity D2 receptors.

To test this theory, researchers needed a radiotracer that could tell the difference between high and low affinity states. But traditional antagonist radiotracers can’t tell the difference between the two states. They bind equally well to both high and low affinity receptors.

Thanks to Dr. Wilson’s pioneering work, researchers can now determine the location and number of specific receptors. “In schizophrenia research, scientists can use this information to show how the brains of people with the illness differ from those of healthy people,” says Dr. Wilson. “This gives a clear picture of the illness and may lead to improved treatment.”

In addition to furthering schizophrenia research, this important discovery also has implications for the study and understanding of movement disorders and addictions.

For Dr. Wilson, the next step is developing more new radiotracers. He has already begun work on new tracers for adenosine A2A receptors and peripheral benzodiazapine receptors. If he’s successful, these tracers will benefit research—and ultimately treatment—in a variety of mental health and substance use areas.

* Wilson, A.A., McCormick, P., Kapur, S., Willeit, M., Garcia, A., Hussey, D. et al. (2005). Radiosynthesis and evaluation of [11C]-(+)-4-propyl-3, 4,4a, 5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-ol as a potential radiotracer for in vivo imaging of the dopamine D2 high-affinity state with positron emission tomography. Journal of Medical Chemistry, 48 (12), 4153–4160.

Radiochemistry Breakthrough Improves Mapping of the Brain

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