Acute Effects of Alcohol on PET Imaging of Phosphodiesterase-4B (PDE4B)
National Institute of Mental Health (NIMH)
Summary
Background: Phosphodiesterase-4B (PDE4B) is a protein in the brain that may play a role in several mental health disorders. Researchers want to know if drinking alcohol increases the binding of a radioactive tracer to PDE4B in the brain because of increased activity and/or amount of the protein. This knowledge may help create new ways to treat people with alcohol use disorder (AUD). Objective: To learn if alcohol increases PDE4B activity in the brain. Eligibility: Healthy people aged 21 to 70 years who drink socially but do not have AUD. They must be enrolled in protocol 14-AA-0181"NIAAA Natural History Protocol". Design: Participants will have up to 4 clinic visits with up to 3 imaging scans of the brain; these will include 1 or 2 positron emission tomography (PET) scans and 1 magnetic resonance imaging (MRI) scan. The first PET scan will be a baseline. Participants will receive a radioactive tracer through a tube inserted into a vein. A second tube will be inserted so that blood can be drawn during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. This visit will take about 6 hours. For the next PET scan, participants will receive alcohol (ethanol) through a tube in a vein until they have a blood alcohol concentration that is equal to the legal driving limit. This is the same as 4 or 5 drinks for most people. After the scan, participants must remain at the clinic for a few hours until their blood alcohol drops. This visit will take 14 to 16 hours. The MRI scan of the brain will take up to 2 hours in a separate clinic visit.
Description
Study Description: Alcohol drinkers with no history of AUD will be enrolled from protocols 14-AA-0181 or 000676. Using the PET radioligand \[18F\]PF-06445974 (Hereafter referred to as \[18F\]PF974) to measure PDE4B binding in the brain, 14-AA-0181 participants will be scanned twice: at baseline and following intravenous administration of ethanol to achieve a target breath alcohol concentration (BrAC) of 0.08 g% (80 mg/dL). For the ethanol condition, alcohol will be administered intravenously prior to PET acquisition to reach and stabilize the target BrAC. PET imaging will then be conducted wi…
Eligibility
- Age range
- 21–70 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: To be eligible to participate in this study, an individual must meet the following criteria: 1. Be enrolled in protocol 14-AA-0181, NIAAA Natural History Protocol. 2. Age 21 - 70 years. 3. Willingness to complete the study including MRI tests. 4. Be in good general health as evidenced by medical history and physical examination. 5. Participants must have had their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists. 6. Able to provide informed consent. EXCLUSION CRITERIA: An indi…
Interventions
- DrugIntravenous Ethanol
Intravenous ethanol infusion before PET Scan
- Drug18F-PF-06445974
Injected IV followed by PET scanning
Location
- National Institutes of Health Clinical CenterBethesda, Maryland