PET radiotracers shed light on drug addiction

Researchers at Brookhaven National Laboratory have developed PET radiotracers to track the movement of various addictive drugs, including cocaine, nicotine, and methamphetamine, as well as to measure the levels of certain neurotransmitters and their receptors in the brain.

PET studies using these radiotracers reveal that addictive drugs elevate levels of the neurotransmitter dopamine, a chemical that helps people experience feelings of pleasure, reward, and motivation. Dopamine also affects physical movement.

The research demonstrates that, through the process of addiction, the brain's ability to respond to pleasure signals becomes depleted as receptors for dopamine are lost. The research also indicates that initial differences in people's dopamine systems may help explain why some people find drugs pleasurable and become addicted while others do not.

One of the challenges for the researchers, led by Joanna Fowler, director of Brookhaven Laboratory's Center for Translational Neuroimaging, has been developing rapid methods for synthesizing the radiotracer compounds. The radioactive isotopes most commonly used, carbon-11 and fluorine-18, have very short half-lives (20 and 110 minutes, respectively).

"We are currently developing new ways to label complex molecules with carbon-11 and fluorine-18 to gain a better understanding of how different drugs of abuse disrupt brain function and how we may be able to treat addiction," Fowler said.

In 1976, Fowler and colleagues synthesized 18F-fluorodeoxyglucose (FDG), the first radiotracer to measure brain glucose metabolism. Fowler also developed another radiotracer that showed how cocaine's distribution in the human brain parallels its effects on behavior, as well as a series of radiotracers to map monoamine oxidase (MAO), a brain enzyme that regulates the levels of other neurotransmitters. Using these agents, she discovered that smokers have reduced levels of MAO in their brains, a finding that may account for some of the behavioral and epidemiological features of smoking, such as the high rate of smoking in individuals with depression and drug addiction.

"The development of radiotracers that can monitor the distribution and kinetics of drugs and receptors in the brain is at the core of understanding the addictive process and finding new ways to help people overcome it," she said.