This study is currently recruiting participants.
PDE4D is a protein in the body that plays a role in thinking and depression. This protein may play a major role in disorders such as Alzheimer disease or major depressive disorder. To learn more about these disorders, researchers want to be able to detect levels of PDE4D in the brain. 11C-JMJ-129 is a new radiotracer (a radioactive substance that highlights parts of the body during imaging scans) that was developed to attach only to PDE4D. However, early human studies showed that the tracer may break down in the body and create byproducts that interfere with the brain signal, making the results harder to interpret. This study will test whether a medication called disulfiram can improve PET imaging with 11C-JMJ-129. Disulfiram blocks an enzyme in the body that may be responsible for breaking down the tracer. By reducing this breakdown, the study aims to improve the quality and accuracy of brain images. The results may help researchers better measure PDE4D in the brain and support future studies of brain disorders.
To test the new radiotracer 11C-JMJ-129, with and/or without disulfiram pretreatment during imaging scans in healthy volunteers.
Healthy people aged 18 years and older who had a screening assessment under protocol 01-M-0254.
Participants will have 1 to 4 clinic visits.
Participants will be screened. They will have a physical exam. They will have blood tests and a test of their heart function.
A positron emission tomography (PET) scan of the whole body. The radiotracer will be injected through a tube placed in a vein in the arm. Participants will lie on a table while a donut-shaped machine passes over them. Blood will be drawn from the arm during this scan.
In Phase 5, disulfiram (500 mg orally) will be administered approximately 20 hours before the post-disulfiram PET scan
A magnetic resonance imaging (MRI) scan of the brain. Participants will lie on a table that slides into a tube.
A PET scan of the brain. These participants will be injected with the radiotracer. They will lie on a table with their head in the scanner.
Participants will be called within 3 days after each PET scan for a check on their health.
INCLUSION CRITERIA:
-Aged 18 years or older.
-Participants must have undergone a screening assessment under protocol 01-M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Participants."
-Healthy based on medical history, physical examination, and laboratory testing.
-Able to provide informed consent.
-Willing and able to complete all study procedures including MRI tests.
-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.
-Agree to adhere to the lifestyle considerations
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
-Clinically significant abnormalities on EKG or laboratory testing. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen).
-Any current Axis I diagnosis.
-History of neurologic illness or injury with the potential to affect study data interpretation.
-History of seizures, other than in childhood and related to fever.
-Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.
-Inability to lie flat on camera bed for at least two hours, including claustrophobia and weight greater than the maximum for the scanner (500 lbs).
-HIV Infection.
-Pregnancy or breast feeding.
-Participants must not have substance use disorder or alcohol use disorder.
-Unable to travel to the NIH.
-Are unable to have an MRI scan (e.g., because of pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel fragments, or metal fragments in the eye.
Additional exclusions for participants receiving disulfiram:
Participants will be excluded if any of the following apply:
a. Current use of, or use within the past 14 days, of metronidazole or paraldehyde.
b. Consumption of alcohol or alcohol-containing products within 24 hours prior to disulfiram administration, or inability/unwillingness to abstain from alcohol containing products for 14 days after administration.
c. History or presence of severe myocardial disease or coronary occlusion. Current or past history of psychotic disorders.
d. Known hypersensitivity to disulfiram or other thiuram derivatives.