Grant: CIHR Fellowship

Alcohol use disorder (AUD) is among the most prevalent psychiatric disorders, and it is the leading preventable cause of death, disease, and disability in Canada. There were 17,098 recorded deaths due to alcohol abuse in 2020 in Canada. It is also important to note that individuals who abuse alcohol are more likely to experience other mental health disorders. This suggests a link between AUD and other mental illness and addictions, which represent a major socioeconomic burden in Canada. The economic cost (healthcare, lost productivity, criminal justice, social assistance costs etc.) of alcohol abuse in Canada was estimated at $19.7 billion in 2020 and accounts for more than 40% of the total costs by substance use disorder that year. As a result, there is an urgent need to develop new tools to improve our understanding of underlying mechanisms in AUD, measure AUD, and facilitate the development of new drugs for treatment of AUD. The reduced expression of a protein called metabotropic glutamate receptor subtype 7 (mGluR7) has been shown to correlate with increased alcohol consumption. Therefore, mGluR7 may play an important role in mediating alcohol consumption. The ability to visualize and quantify mGluR7 in the brain will aid in: 1) measuring AUD, 2) accelerating the discovery of new drugs for treating AUD, and 3) monitoring and quantitatively measuring how patients respond to AUD treatments. Positron emission tomography (PET) imaging is a non-invasive technique that can visualize physiology and biochemical processes in a living body by utilizing small molecules that contain a radioactive element, called radiotracers. This project describes the preparation of the first brain-penetrant radiotracer for PET imaging of mGluR7 in animal models of alcohol consumption. The successful synthesis of this tracer and its preclinical imaging would enable the visualization and quantitative measurement of mGluR7 changes in alcohol addiction and clinical therapy for the first time.